rivalstoremicade reach major european markets - · pdf file ·...

27 February 2015

Cipla gains ground in 2North Africa via JVsActavis intends to adopt Allergan name 3Teva plans to set up a biologicals facility 4Wockhardt resolves faults at US factory 5Sawai sees turnover rise 6faster than profitAurobindo venture to target PCV vaccines 7Growth in US helps Zydus to advance 8Lannett turns gaze toWestern Europe 9Russia and Ukraine hit Richter’s results 10Protopic rival peps Perrigo’s turnover 11Towa cuts its costs to improve margins 12Siegfried sorts out FDA Hameln letter 13Glenmark grows its sales as profits slide 14

MARKET NEWS 15

FDA reopens debate on label change rule15France must address declining sales trend 16Canada will require 17shortage notificationInput is invited over US interchangeability 19OGD sets target forANDA action dates 20

PRODUCT NEWS 21

Lupin enlists Celon for American Advair 21Mylan must wait for 22esomeprazole in USHospira and Pfenex develop ranibizumab23Lupin wins appeal on US Trizivir patent 24Pregabalin dispute will persist in the UK25Spain’s Kern Pharma 26introduces infliximabMomenta is open to abatacept options 27Norway enjoys steep infliximab price cut 29

FEATURES 32

Pfizer eyes two top spots 32with Hospira acquisition

REGULARS

PipelineWatch – Remicade 28Events – Our regular listing 30PriceWatch UK – UK pricing trends 31People – Bayer’s Brandicourt 34leads Sanofi as CEO

COMPANY NEWS 2

Rivals to the Remicade (infliximab) monoclonal antibody marketed by Janssen andMerck are now available throughout Europe after Celltrion and Hospira seized on

expiries of paediatric extensions to supplementary protection certificates (SPCs) duringFebruary to enter the market (see pages 24 and 28).

On 25 February, Celltrion announced launches of its Remsima biosimilar through partnerssuch as Kern Pharma and Mundipharma (see page 26) in Austria, Belgium, Denmark, France,Germany and Greece, as well as in Italy, Luxembourg, the Netherlands, Spain, Sweden and theUK. The treatment for autoimmune diseases was now available in 31 countries, the firm noted.

Hospira has launched its Inflectra (infliximab) biosimilar monoclonal antibody inseveral European markets, including Austria, Denmark, France, Germany, Greece, Italy,Luxembourg, the Netherlands, Spain and Sweden. “Inflectra is now available in 24 Europeancountries,” noted the injectables specialist, which already markets infliximab in Central andEastern Europe, as well as in some smaller Western European markets.

In September 2013, the European Commission authorised Remsima and Inflectra for treatinginflammatory conditions including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis,adult and paediatric Crohn’s disease, adult and paediatric ulcerative colitis and plaque psoriasis.

Global Remicade turnover ahead by 2.9% to US$6.87 billion last year reported by Janssen’sparent group, Johnson & Johnson, included US$1.64 billion in non-US International markets.

On 17 March, the US Food and Drug Administration’s (FDA’s) Arthritis AdvisoryCommittee will hold a public meeting to discuss a biologics license application (BLA) thathas been submitted by Celltrion for its CT-P13 proposed rival to Remicade.

US patent 6,284,471 protecting Remicade until September 2018 has just been rejectedupon re-examination by the US Patent and Trademark Office (USPTO). The ‘471 patent –which covers assays using anti-tumour necrosis factor (TNF) antibodies – was one of threepatents for which Celltrion sought a declaratory judgement of non-infringement last year.However, the two parties settled the litigation on confidential terms. G

Pfizer has agreed to pay around US$17 billion, including assumed debt, to acquireinjectables specialist Hospira. The US$90-per-share deal has been approved unanimously

by both firms’ boards and is scheduled to close during the second half of this year, subject toantitrust clearance and approval by Hospira’s shareholders. The agreement – which representsa 39% premium on Hospira’s closing price on 4 February, and around four-times Hospira’sannual sales – includes a US$500 million break-up fee.

“Hospira’s business aligns well with our new commercial structure and is an excellentstrategic fit for our Global Established Pharmaceutical (GEP) business, which will benefitfrom a significantly enhanced product portfolio in growing markets,” commented Pfizer’schairman and chief executive officer, Ian Read.

“The expanded portfolio of sterile injectable pharmaceuticals, composed of Hospira’sbroad generic sterile injectables product line, including acute-care and oncology injectables,with a number of differentiated presentations, as well as its biosimilars portfolio, combinedwith GEP’s branded sterile injectables, including anti-infectives, anti-inflammatories andcytotoxics, will create a leading global sterile injectables business,” Pfizer maintained. G

For details of the deal, turn to page 32.

Rivals to Remicade reachmajor European markets

Pfizer pays US$17bn for Hospira

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Cipla has broadened its presence in North Africa by agreeing toestablish joint ventures with the company’s existing partners in

Algeria and Morocco.Through its UK subsidiary, Cipla EU, the Indian firm will hold a

40% stake in a venture it is creating with its Algerian partner, Biopharm,and a 60% stake in a similar scheme it is establishing with CooperPharma and The Pharmaceutical Institute, Cipla’s allies in Morocco.

Both ventures – which are subject to certain regulatory approvals –will be used as a vehicle to market Cipla’s respiratory franchise inthe respective countries, and will include the companies supplyingfunds to build local manufacturing facilities. The Indian firm isexpected to contribute US$6 million of a total US$15 million inAlgeria, while it will pour up to US$15 million into its scheme inMorocco, where Cipla will also promote its neurology drugs.

Meanwhile, Cipla has agreed to acquire for Rs960 million(US$15.4 million) a 60% stake in privately-owned Indian firm JayPrecision Pharma, an existing supplier of Cipla’s respiratory devices.

Jay Precision – which boasts a manufacturing facility in Vasai,Maharashtra – had sales of around Rs300 million in its financial yearended 31 March 2014. Slated to close by the end of next month, thetransaction was aimed at “integrating the value chain and will serveas a platform for the development of next-generation respiratorydevices”, Cipla said.

Indian sales increased by 14%In Cipla’s financial third quarter ended 31 December 2014,

domestic sales rising by 14.2% to Rs12.0 billion helped overcomesingle-digit turnover slips from exports of active pharmaceuticalingredients (APIs) and finished-dose formulations as the Indiancompany improved its sales by 6.5% to Rs27.7 billion (see Figure 1).

However, the Indian firm’s export sales could soon be bolsteredafter Cipla announced that it had “gone live” in North America, andhad subsequently introduced its first ‘own-label’ products in the regionincluding doxycycline, meloxicam, topiramate and valaciclovir.

Moreover, Cipla has revealed that it will be supplying esomeprazoleactive pharmaceutical ingredient (API) and finished-dose formulation

to Teva, following the Israeli group’s recent nod for the first USgeneric rival to AstraZeneca’s Nexium blockbuster (Generics bulletin,6 February 2015, page 17).

Elsewhere, Cipla’s in-licensing agreement with Teva in SouthAfrica though its local Cipla Medpro affiliate for access to “65 newmolecules” (Generics bulletin, 17 October 2014, page 6) has receivedclearance from the country’s Competition Commission. The Indianfirm has also just been awarded a US$189 million share in a GlobalFund antiretroviral tender (see page 27).

Meanwhile, the founder of the Serum Institute of India, CyrusPoonwalla, has revealed that the company and Cipla had held initialmerger talks following their agreement covering paediatric vaccinesin Europe that was struck late last year (Generics bulletin, 5December 2014, page 6). “We [Serum Institute] could never go upfor sale,” he said, “but we could merge with a company, for exampleCipla…there is a small chance that could happen.”

“We first have to see if the initial partnership bears fruit,”Poonwalla added. “If it moves in the right direction, maybe we willtake it to the next stage.”

A marginal increase in Cipla’s expenses was offset by the firm’s6.5% sales rise, as its pre-tax profit rose by 8.3% to Rs4.28 billion. G

COMPANY NEWS

2 GENERICS bulletin 27 February 2015

27 February 2015 Issue 226

Editor: Aidan FryDeputy Editor: DavidWallaceAssistant Editor: Liudmila KotkoBusiness Reporter: Dean RudgeProduction Controller: Debi MinalProduction Editor: Jenna MeredithDirector of Subscriptions: Val DavisAwards Manager: Natalie CornwellManaging Director: Mike Rice

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Cipla gains ground in North Africa via JVsSTRATEGIC ALLIANCES/THIRD-QUARTER RESULTS

Third-quarter sales* Change Proportion(Rs millions) (%) of total (%)

Formulations 12,750 -6.2 46APIs 1,510 -4.4 5Exports 14,260 -6.1 52

India 11,990 +14.2 43

Other 1,410 – 5

Cipla 27,650 +6.5 100

* rounded to nearest Rs10 million

Figure 1: Breakdown of Cipla’s net sales in its financial third quarter ended 31December 2014 (Source – Cipla)

Gen 27-02-15 Pgs.2-14_Layout 1 25/02/2015 18:33

Claris Lifesciences has quashed media speculation that it isconsidering selling its generic sterile injectables business,

Claris Injectables.Responding to an article that appeared in India’s Economic Times

newspaper on 12 February, Claris announced in a disclosure to theBombay Stock Exchange (BSE): “At present we are not negotiatingthe sale of a stake in the injectables business, and the board ofdirectors of the company has neither considered nor taken anydecision in this regard.”

According to the Times’ article, as many as seven companies– Cipla, Dr Reddy’s, Lupin, Pfizer, Sandoz, Sun and Zydus Cadila –had shown some level of interest in acquiring Claris Injectables foraround Rs25-30 billion (US$402-US$482 million), with severalhaving submitted initial bids.

Operating three manufacturing facilities that have been approvedby various regulatory authorities – including from the US, UK andAustralia – at a site in Ahmedabad, India, Claris Injectables offersa wide portfolio of injectables across multiple delivery systems. Theoperation – which Claris created last year by transferring its specialtyinjectables business to a subsidiary – also spans product development,regulatory affairs and sales and marketing units.

Claris Injectables forms the bulk of Claris’ operations, after theIndian group sold an 80% stake in its infusion business in India andother emerging markets to Japanese players Otsuka and Mitsui twoyears ago (Generics bulletin, 9 August 2013, page 10).

The Indian group said its injectables sales grew by “approximately”62% to Rs4.06 billion last year. Including a contribution made by theIndian firm’s minority stake in its infusion business, group turnoverreached Rs7.14 billion. Emerging markets accounted for half of thattotal, the US 23%, and other regulated markets the remaining 27%.

Having filed nine abbreviated new drug applications (ANDAs)during 2014, the injectables unit ended the year with 13 of its 37filings approved, and 24 pending review. The unit – which generatedearnings before interest, tax, depreciation and amortisation (EBITDA)of Rs1.49 billion last year – plans to file 18 ANDAs this year, inline with its target “to have a total of 100 ANDAs in the US withinthe next three years”. G

COMPANY NEWS

3GENERICS bulletin27 February 2015

Teva has identified, following a voluntary global investigationinto its business practices, potential issues in “Russia, certain

Eastern European countries, certain Latin American countries andother countries” that “likely constitute” violation of the US ForeignCorrupt Practices Act (FCPA).

“In connection with our investigation, we have also becomeaware that affiliates in certain countries provided to local authoritiesinaccurate or altered information relating to marketing or promotionalpractices,” the Israeli group admitted.

Noting that its investigation was expected to continue at least untilthe end of the year, Teva stressed that it had “brought and continueto bring these issues to the attention of the Securities and ExchangeCommission (SEC) and the US Department of Justice (DoJ)”. Anyfines or disgorged profits could be “material”, it acknowledged. G

Claris rejects talkof injectables sale

BUSINESS STRATEGY/ANNUAL RESULTS

Actavis plans to adopt the Allergan name for its corporate identityand branded portfolio once it completes its US$66 billion takeover

of the ophthalmics specialist in the next few weeks. However, thegroup will retain the Actavis name “for select geographic regions andproduct portfolios”. The change in corporate name is subject toshareholder approval.

“By adopting the Allergan name for the corporation, we willensure that our corporate identity reflects the dramatic evolution ofour company,” explained president and chief executive officer BrentSaunders. “For more than 65 years, the Allergan name has representedinnovation in branded pharmaceuticals.”

“The Actavis name has represented our global commitment toleadership in generic, branded generic and OTC pharmaceuticals andto increased access to more affordable prescription medicine,” hecontinued. “Retaining the Actavis name reflects this heritage, as wellas the considerable equity of the Actavis name with our customersin key markets around the world.”

Actavis – which has recently unveiled its senior managementteam following the Allergan deal (see page 35) – increased its turnover

last year by 50.5% to US$13.1 billion due to a full-year contributionfrom Warner Chilcott and consolidating Forest from 1 July 2014.

International sales outside of North America grew by 2.8% toUS$2.57 billion, due to a US$123 million input from Forest’s non-US brands and a contribution from Warner Chilcott that almost trebledto US$181 million. Those factors were offset in part by a US$237million decrease from the Western European commercial operationsthat the group divested to Aurobindo on 1 April last year. At the sametime, Actavis closed its acquisition of Thai generics specialist Silom(Generics bulletin, 18 April 2014, page 3).

“In our North American Generics business, strong results weredriven by continued performance of our generic versions of Lidoderm(lidocaine) and Concerta (methylphenidate), and fourth-quarter launchesof generic versions of Intuniv (guanfacine) and Celebrex (celecoxib),”Saunders stated. Sales rose by 6.6% to US$4.17 billion (see Figure 1).

North American Brands turnover reached US$4.63 billion, whilehigher prices and volumes pushed up revenues by the group’s USAnda Distribution business by 40.7% to US$1.68 billion.

Acquisition-related charges – including a US$190 milliongoodwill write-off on the Pharmatech drug-delivery business thatActavis has agreed to sell to investment firm TPG – caused the groupto post a US$1.27 billion operating loss. G

Actavis intends toadopt Allergan name

BUSINESS STRATEGY/ANNUAL RESULTS

Teva reports likely corruptionINVESTIGATIONS

Business Annual sales Change Operatingsegment (US$ millions) (%) margin (%)

North American Generics 4,174 +6.6 –International 2,574 +2.8 –Generics/International 6,747 +5.1 32.0

North American Brands 4,631 +335.9 20.0

ANDA Distribution 1,684 +40.7 4.7

Actavis 13,062 +50.5 –*

* operating loss of US$1.27 billion includes US$4.43 billionof expenses not attributed to business segments

Figure 1: Breakdown of Cipla’s net sales in its financial third quarter ended 31December 2014 (Source – Cipla)

Gen 27-02-15 Pgs.2-14_Layout 1 25/02/2015 18:33

COMPANY NEWS


Teva is developing a plan to establish a “significant” biologicsproduction facility, according to its chief executive officer, Erez

Vigodman. “That is one gap we have. And we will over time also crafta plan to deal with go-to-market capability. We might then pursue apartner to accelerate the pace of execution,” he told investors.

Operations chief Carlo De Notaristefani noted that the group’scurrent mammalian and microbial manufacturing capacity was “at asmall scale”. “We need to expand that, and we are currently assessingthe best location to do this,” he revealed.

Commenting on Teva’s biosimilars strategy, Generics head SiggiOlafsson admitted he would “love to have more” candidates in thebiosimilars second wave, comprising mainly monoclonal antibodies.The first wave of growth hormones, epoetins and filgrastims weregenerating annual sales of US$200-US$300 million for Teva, he noted.

“We need a little bit bigger pipeline in wave two to be a realplayer in the 2020-2021 timeframe,” Olafsson recognised. “We arelooking for the right assets and partner to be a real player in themarket in five to six years.”

Options included acquisitions, joint ventures and co-developmentdeals, he explained. While more than 100 companies claimed to haveusable second-wave projects, he said Teva had limited that selectionto “probably five to 10 companies that really have strong assets”.

Teva’s combination of generics and specialty brands expertisewas a key commercial advantage, Olafsson maintained. “We do notexpect any interchangeability, at least in the first few years,” he said.As an example of Teva’s ability to market biologics, he cited the firm’sGranix (tbo-filgrastim) brand – authorised as a standalone biologic –in the US, which had captured more than a 15% market share.

Olafsson said Teva was also expanding its presence in genericinjectables, especially in long-acting formulations. Having tackledmanufacturing issues in recent years, the company was “re-enteringthe market” in the US, he said, with recent launches such asenoxaparin and linezolid set to push up US injectables turnover from“just over US$100 million” in 2014 to at least US$300 million thisyear (Generics bulletin, 16 January 2015, page 29). Teva’s globalinjectables turnover was around US$500-US$700 million he added.

Noting Pfizer’s US$17 billion planned takeover of Hospira,Olafsson said Teva intended to be a niche US injectables player.“We are not competing on the big-volume antibiotics and oncologyproducts,” he said. Rather, he added, Teva was focusing on hard-to-make injectables such as a version of Luitpold’s Venofer (iron sucrose).

A 6% sales rise to US$4.42 billion in US Generics sales lastyear failed to compensate fully for declines in Teva’s Europe andRest of the World regions as its global Generics turnover dipped by1% to US$9.81 billion (see Figure 1). In local currencies, globalsales – including sales of active pharmaceutical ingredients (APIs)to third parties that stalled at US$724 million – edged up by 1%.

Exclusive or first-to-market launches of generic Xeloda(capecitabine) and Lovaza (omega-3 ethyl esters) contributed to theUS gains, as did introducing a rival to Evista (raloxifene). Launchinginjectable carboplatin and enoxaparin, as well as celecoxib capsulesand buprenorphine/naloxone sublingual tablets helped to maintainfourth-quarter US Generics sales at US$1.18 billion. But declinesof 16% in Europe and of 12% in the Rest of the World – due in partto exchange-rate shifts – reduced global Generics turnover by 8%to US$2.47 billion in the fourth quarter.

Full-year Generics sales in Teva’s 36 European countries – theEuropean Union, Norway, Switzerland, Albania and the countriesof the former Yugoslavia – fell by 6% to US$3.15 billion. Teva saidthe 7% local-currency decrease was “mainly due to our focus on

profitable business as well as market dynamics in certain countriesincluding Germany, France and Spain”.

Olafsson said Teva’s team in Germany was “doing extremelywell”. While local Generics sales were down by 13% last year on“lower participation in the tender market and increasing pressureon prices in the retail generics segment”, the team had successfullylaunched several respiratory brands. French Generics sales fell by 12%amid “increasing competition” and revised rules on pharmacy discounts.

“We really do not want to go too much into the tender business inSpain,” Olafsson added. The firm said a 13% Generics slide in Spainwas “due mainly to the impact of the implementation of newcommercial policies, and the increasing scope of the tendering systemin the Andalucía region, in which we chose not to participate”.

Olafsson said “the UK did very well”, seizing on local supplyshortages to raise local sales by 1%. And “improvements in our supplymanagement” helped Italian sales to grow by 12%, while turnoverin Switzerland rose by 4% on higher volumes driven by recent launches.

A reported 5% Generics decline to US$2.25 billion in the group’sRest of the World region equated to 4% local-currency growth. InRussia, a 14% slide translated to a 3% local-currency gain as highersales of branded generics outweighed lower revenues from governmenttenders. Canadian sales rose by 5%, or by 12% in local-currencyterms, aided by reversing a pricing reserve. But “quality and supplyissues”, as well as price cuts imposed in April 2014, cut turnover inJapan by a tenth, or by 3% in the local currency.

Higher sales in the US and Canada, as well as better marginson third-party API sales, boosted Teva’s Generics gross margin by2.1 percentage points to 43.3%. Research and development costsrose by 5% to US$517 million, but sales and marketing expensesfell by 18% to US$1.58 billion, due in part to lower royalty paymentson US sales of generic Pulmicort (budesonide). A 29% gain to US$2.15billion in the Generics segment’s operating profit – excludingunallocated corporate expenses – improved the segment’s operatingmargin by 5.1 points to 21.9%.

The Israeli group’s overall performance followed a similar trend.Operating profit more than doubled to US$3.95 billion following aprior-year charge to settle damages for the firm’s at-risk US launchof pantoprazole. But turnover stagnated at US$20.3 billion, asCopaxone (glatiramer acetate) accounted for almost half of SpecialtyMedicines sales ahead by 2% to US$8.56 billion. G

Teva plans to set up a biologicals facilityBUSINESS STRATEGY/ANNUAL RESULTS

Annual sales Change Proportion(US$ millions) (%) of total (%)

US 4,418 +6 22Europe 3,148 -6 16Rest of the World 2,248 -5 11Generic Medicines 9,814 -1 48

Copaxone/CNS 5,575 +1 28Oncology 1,180 +17 6Respiratory 957 -1 5Women’s Health 504 -1 2Others 344 -5 2Specialty Medicines 8,560 +2 42

OTC/Other 1,898 -6 9

Teva 20,272 ±0 100

Figure 1: Breakdown by business segment of Teva Pharmacetical Industries’sales in 2014 (Source – Teva)

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COMPANY NEWS


Failing to ensure laboratory records include complete data, toexercise appropriate controls over computer systems and to

establish and follow appropriate written procedures are among the“serious current good manufacturing practice (cGMP) violations”listed in a warning letter that the US Food and Drug Administration(FDA) has issued to the Apotex Research Private Limited (ARPL)finished-dose facility in Bommasandra near Bangalore, India.

“The FDA’s concern pertains to the practice of disregardingfailing results, conducting trial injections and retesting productswithout any investigation,” the letter states. “We are also concernedthat you do not have documentation to support your decision to retestsamples of lots that had initially failed to meet specifications, andyou allowed manufacturing activities to occur without the oversightof your quality unit.”

Noting that some of the deficiencies found during an inspectionof the ARPL site conducted in June and July last year were repeatobservations from a 2010 warning letter, the FDA tells Apotex toprovide “a comprehensive evaluation of the extent of the inaccuracyof recorded and reported data” along with a risk assessment of theeffects of the observed failures and a management strategy for globalcorrective and preventive action plans.

“The inspection of your facility documented multiple incidentsof performing ‘trial’ testing of samples, disregarding test resultsand reporting only those results from additional tests conducted,”the letter states. In particular, it accuses the firm of using only “themost favourable result” from impurity testing, while quality-controlpersonnel “created unauthorised folders on laboratorycomputerised systems with appropriate oversight”.

“ARPL’s inability to prevent and detect poor recordkeepingpractices raises serious concerns regarding the quality system in placeat the time of the inspection,” objects the FDA.

Pointing out that it had notified the firm of the agency’s concernabout trial injections during a January 2014 inspection of theApotex Pharmachem bulk-drugs unit at Bommasandra, the FDAstates: “Our findings during this inspection suggest that correctiveactions were not implemented globally.” As a result of that inspection,the FDA issued a warning letter to Apotex Pharmachem midwaythrough last year (Generics bulletin, 11 July 2014, page 2), followedby an import alert. In response, Health Canada asked Apotex toquarantine products made at the ARPL plant (Generics bulletin, 3October 2014, page 3).

At that time, Apotex insisted it was “absolutely confident in thesafety and effectiveness of all our products throughout the entiretyof our manufacturing and testing processes, regardless of where itwas manufactured”.

Meanwhile, the FDA has also issued a warning letter to MicroLabs’ facility in Verna, India, following an inspection in May 2014.The cGMP deficiencies listed include: failure to ensure thatlaboratory records include complete data derived from necessarytesting; failure to exercise appropriate controls over computersystems; and failure to record or justify deviations from requiredlaboratory-control mechanisms.

As in the Apotex warning letter, the FDA took issue withunauthorised ‘trial’ high performance liquid chromatography (HPLC)injections prior to injections used in reported test results. The agencyalso pulled up the Indian company for filing field alert reports offailed impurity results almost a month late. G

Wockhardt says it has “resolved all issues” at its Morton Grovefacility in Illinois, US, which last year led the US Food and

Drug Administration (FDA) to issue the Indian firm with ‘Form483’ observations for deficiencies related to quality controls andprocedures (Generics bulletin, 5 September 2014, page 4).

“Our responses to the [Form] 483…have been found satisfactoryby the FDA and operations continue as normal,” the Indian firm’smanaging director, Murtaza Khorakiwala, told investors. “We[appointed] a new leadership in quality function [six months ago],and then we had a one-on-one meeting with the FDA,” he revealed.“[The agency] wanted some more clarification, but they very clearlyindicated that they intend to take no further action.”

The firm’s Morton Grove facility has increased in importanceto Wockhardt since the FDA barred US imports from its IndianChikalthana and Waluj plants in 2013 (Generics bulletin, 6 December2013, page 3). However, Khorakiwala revealed, Wockhardt hadinvited the FDA to begin inspections of all its facilities. Thisincluded Wockhardt’s newest facility in Shendra, India, from wherethe company has filed the “majority” of its abbreviated new drugapplications (ANDAs) over the past two years.

Meanwhile, the UK’s Medicines and Healthcare productsRegulatory Agency (MHRA) has allowed Wockhardt to beginimporting products from Chikalthana to the UK again after it removeda statement of non-compliance from the site.

The agency had only just extended that statement of non-complianceto cover all drugs manufactured at Chikalthana (Generics bulletin,6 February 2015, page 2), having two years ago issued the facilitywith a restricted good manufacturing practice (GMP) certificate, toavoid market shortages, following observations of criticaldeficiencies (Generics bulletin, 18 October 2013, page 6).

In its financial third quarter ended 31 December 2014, a UKsales boom offset depleted turnover in the US caused by thosemanufacturing issues as Wockhardt’s sales rose by 12% to Rs13.8billion (US$223 million). UK turnover more than doubled – increasingby 141% to Rs6.30 billion – while sales in the US tumbled by 48%to Rs2.82 billion (see Figure 1).

That UK turnover surge also comfortably offset sales dips of16% to Rs330 million and 37% to Rs390 million in France and Irelandrespectively. But Wockhardt’s turnover in India and Emerging Marketsrose by almost a fifth to Rs3.86 billion, as the Indian firm launchedseven products in its domestic market during the quarter.

Despite ramping up research and development spending by morethan a fifth to Rs1.19 billion, Wockhardt’s pre-tax profit improvedby 29% to Rs4.08 billion. G

FDA warns Apotexover Indian facility

Wockhardt resolvesfaults at US factory

MANUFACTURING/THIRD-QUARTER RESULTS

Region Third-quarter sales Change Proportion(Rs millions*) (%) of total (%)

Europe 7,140 +92 52

India/Emerging 3,860 +18 28

US 2,820 -48 20

Wockhardt 13,820 +12 100

* rounded to the nearest Rs10 million

Figure 1: Breakdown by region of Wockhardt’s sales in its financial third quarterended 31 December 2014 (Source – Wockhardt)

MANUFACTURING

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COMPANY NEWS


Sun Pharma blamed “temporary supply constraints arising fromremediation efforts” for its net sales stalling at Rs42.8 billion

(US$688 million) in the Indian group’s financial third quarter ended31 December 2014. The company – which is awaiting Indian courtclearance to complete its US$4 billion takeover of Ranbaxy – posteda 9% fall in pre-tax profit to Rs18.5 billion.

Managing director Dilip Shanghvi said he expected supplies fromthe firm’s formulations facility in Halol, India, to improve as Sunimplemented corrective actions to deficiencies identified during aninspection by the US Food and Drug Administration (FDA) inSeptember last year (Generics bulletin, 5 December 2014, page 3).“We have given a detailed response, and we are meeting all the datesthat we shared with the FDA,” he told investors.

Shanghvi blamed “temporary supply constraints at Halol, the lossof exclusivity for generic Prandin (repaglinide) and a significantdecline in doxycycline sales” for US Formulations turnover slidingby 4.4% to Rs25.6 billion. The local-currency decline was 5% toUS$413 million, even though the group’s Taro affiliate – in whichSun holds a 69% stake – posted an 11.3% sales rise to US$238 million,despite “a volume decrease across all markets”.

“Temporary supply constraints arising from remediation efforts”also contributed to Formulations turnover in Sun’s Rest of the Worldregion tumbling by 14.7% to Rs4.44 billion (see Figure 1). Andexcluding Taro’s non-US sales, turnover in the region plunged by 29%.

But the US and Rest of the World declines were cancelled out bythe Indian group improving branded generics turnover in its domesticmarket by 21.4% to Rs11.5 billion, aided by 15 product launches since

April 2014. Bulk Drugs sales to third parties rose by 4.0% to Rs1.81billion as Sun stepped up internal vertical integration for key products.

Supply constraints and increased compliance costs at Halol, aswell as integration planning ahead of the planned closure of theRanbaxy deal by the end of March, contributed to a 3% slide toRs19.1 billion in group earnings before interest, tax, depreciationand amortisation (EBITDA).

Sun’s research and development spending reached Rs3.89 billion,or just over 9% of sales, as the firm made “significant investments”in clinical development of tildrakizumab, a psoriasis monoclonalantibody recently licensed from Merck & Co.

Having submitted 19 abbreviated new drug applications (ANDAs)between April and December 2014 – and received 14 approvals –Sun ended the quarter with 358 approved ANDAs and 131 pendingFDA final clearance, including 11 tentative approvals. G

Government initiatives to increase the use of generics werecredited by Sawai Pharmaceutical as the primary driver for its

sales increasing by 18.0% to ¥80.2 billion (US$669 million) in thefirst nine months of its financial year ending 31 March 2015. Butduring that period, the Japanese firm’s operating profit grew by just2.4% to ¥17.4 billion, giving it an operating margin 3.3 percentagepoints lower at 21.7%.

Recent price revisions – mandated by Japan’s National HealthInsurance (NHI) system – and “growing sales of low-priced products”explained the disparity between the growth in sales and operatingprofit, Sawai said. Volumes had increased by 26.9%, the companyobserved, compared to the 18.0% value rise.

Cardiovascular drugs enjoyed a sales rise of just under a fifthto ¥24.5 billion, or around 30% of Sawai’s turnover. The categoryaccounted for a quarter of Sawai’s sales by volume, as the numberof units sold advanced by a third. Meanwhile, volume rises of 42.5%for blood products and 59.3% for respiratory drugs translated to valuerises of 34.8% to ¥9.13 billion and 46.6% to ¥2.27 billion respectively.

Sawai envisages annual sales ahead by 18.0% to ¥106 billion andan operating profit that will grow by a tenth to ¥21.0 billion. G

Sun’s sales stall onconstraints in supply

THIRD-QUARTER RESULTS

Sawai sees turnoverrise faster than profit

NINE-MONTH RESULTS

Third-quarter sales Change Proportion(Rs millions) (%) of total (%)

US 25,602 -4.4 60India 11,500 +21.4 27Rest of the World 4,444 -14.7 10Formulations 41,546 +0.2 97

Bulk Drugs 1,811 +4.0 4

Other/eliminations -562 – -1

Sun Pharma 42,795 -0.2 100

Figure 1: Breakdown by region and business of Sun Pharma’s gross sales in itsfinancial third quarter ended 31 December 2014 (Source – Sun Pharma)

Valeant has agreed to buy Salix Pharmaceuticals in deal that valuesthe US gastrointestinal specialist at US$14.5 billion. The US$158-

per-share cash transaction is scheduled to close during the secondquarter of this year.

“The growing gastrointestinal market has attractive fundamentals,and Salix has a portfolio of terrific products that are outpacing themarket in terms of volume growth, [as well as] a promising near-termpipeline of innovative products,” commented Valeant’s chairman andchief executive officer, Michael Pearson.

Meanwhile, Valeant has just closed a US$400 million deal to buyseveral assets of bankrupt Provenge (sipuleucel-T) provider Dendreon.

Last year, a full-year contribution from its Bausch & Lombacquisition lifted Valeant’s group turnover by 43% to US$8.26 billion.The firm said this equated to 13% ‘same-store’ organic growth.

On the same basis, the group’s Emerging Markets sales rose by8%. As Figure 1 shows, the reported increase was 42% to US$2.10billion, as turnover in the firm’s Asia/Africa region more than doubled.“We continued to see strong organic growth in several emerging marketssuch as China, the Middle East and Russia,” Pearson stated. G

MERGERS & ACQUISITIONS/ANNUAL RESULTS

Valeant aims to acquire Salix

Annual sales Change Proportion(US$ millions) (%) of total (%)

Developed markets 6,167 +44 75

Europe/Middle East 1,087 +34 13Asia/Africa 574 +110 7Latin America 435 +11 5Emerging markets 2,096 +42 25

Valeant 8,264 +43 100

Figure 1: Breakdown of Valeant’s sales in 2014 (Source – Valeant)

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COMPANY NEWS


Julphar has established a direct presence in Bangladesh by acquiring amajority stake in its local partner, RAK Pharmaceuticals, for US$9.5

million. The two firms, the group based in the United Arab Emirates(UAE) pointed out, had held a “long-term strategic alliance” thatcovered a technology-transfer and marketing deal for several products.

“RAK is a relatively young, fresh company with solidinfrastructure, growth rates and a healthy pipeline,” commentedJulphar’s chief executive officer, Ayman Sahli. The deal, he said,would help the firm to serve 160 million people and a Bangladeshipharma market valued at around US$1.3 billion.

“The stable investment outlook and the growing healthcare needsof a large, mostly underserved population make Bangladesh anattactive market for investors,” Sahli added. “Healthcare plays amajor role in the expanding economy of Bangladesh, and with thiscomes a clear need for increased manufacturing.”

A subsidiary of RAK Ceramics, RAK Pharma operatesproduction facilities 42 kilometres north of Dhaka, Bangladesh, ona complex that includes a separate unit for cephalosporin antibioticsin tablet, capsule and dry-syrup forms. Having started marketingoperations in mid-2009, the company has built up a broad portfolioof more than 100 branded generics that in 2013 generated a turnoverof US$5.7 million, representing growth of 24%.

Having in 2012 invested US$150 million in a manufacturingfacility in the UAE dedicated to producing raw materials for insulinsand biosimilars, Julphar in 2013 launched its first internationalfinished-dose facility in Ethiopia with local partner Medtech,“initiatinga global expansion strategy to increase manufacturing capabilitiesacross its major markets”.

“We are in the early stages of expanding our manufacturingcapabilities in Ethiopia,” the group’s director of Sub-SaharanAfrica, Steve Gravenor, told Generics bulletin. “We plan to build anew fill-and-finish facility which will produce insulin, using our ownactive pharmaceutical ingredient (API) manufactured in the UAE.”

“Our short-term aim is to expand our manufacturing base inEthiopia, to supply domestic and eventually export markets. Furtherabroad, Julphar is exploring partnerships with local players fromprivate and government sectors,” Gravenor explained, adding thatthis strategy fitted well with the African Union Commission’sPharmaceutical Manufacturing Plan (PMP) to expand and improvethe quality and scale of pharmaceutical production in the continent.

Meanwhile, Julphar – which achieved a turnover of AED1.4billion (US$381 million) last year – is constructing a facility in Jeddah,Saudi Arabia, with local partner Cigalah Group. G

Aurobindo Pharma plans to set up a joint venture with TergeneBiotech, an Indian company that is developing a pneumococcal

conjugate vaccine (PCV). “Aurobindo will hold a majority stake inthe joint venture and will fund the product development in a phasedmanner spanning three years,” the Indian firm stated, adding thatthe commercially-available PCV had “limited competition and aglobal branded market of more than US$5 billion”.

“It will take around three years for us to get the developmentcompleted and the facility up and running,” noted Aurobindo’smanaging director N Govindarajan. “Initially our focus will be ontender markets.” “This is an area that is much tougher than typicaldevelopment projects,” he commented, highlighting limited competition.

Stronger Formulations sales, driven in part by having acquiredActavis’ commercial operations in Western Europe, enabled Aurobindoto raise its group turnover by 47.9% to Rs31.7 billion (US$513 million)in its financial third quarter ended 31 December 2014. Formulationsturnover ahead by 76.2% to Rs25.3 billion more than offset a 9.4%fall to Rs6.74 billion in sales of active pharmaceutical ingredients(APIs) due to lower semi-synthetic and non-betalactam revenues.

Incorporating the former Actavis operations had strengthened

Aurobindo’s presence in Germany, the Netherlands, Portugal andSpain, Govindarajan pointed out, while providing access to Belgium,France and Italy. “The revenue and profit numbers for the integratedEuropean operations have been in line with our expectations,” he stated.

Aurobindo’s European Formulations sales showed an almostsix-fold rise to Rs8.61 billion, accounting for more than a quarterof group turnover. Another 38% came from US Formulations turnoverrising by 29.0% to Rs12.0 billion (see Figure 1) on market-sharegains and “opportunistic price increases”.

The firm’s AuroMedics US injectables unit – which has 45 filespending approval – contributed sales ahead by 71% to US$18 million.

Having incorporated its US$133 million purchase of nutraceuticalscompany Natrol from 4 December, Aurobindo intends to expandthe business – which has annual sales of around US$100 million –beyond the US (Generics bulletin, 5 December 2014, page 5).

Formulations sales in the Rest of the World region stalled atRs1.34 billion as the company switched focus in South Africa fromtenders to the private market. Antiretroviral Formulations turnoverclimbed by 51.5% to Rs3.34 billion as the firm won “notable tenders”.

Higher raw-material and operating expenses caused the Indiangroup’s pre-tax profit to slip by 2.0% to Rs5.39 billion. G

Julphar buys stake inBangladeshi partner

MERGERS & ACQUISITIONS

Aurobindo venture totarget PCV vaccines

BUSINESS STRATEGY/THIRD-QUARTER RESULTS

Business Third-quarter sales Change Proportionsegment (Rs millions) (%) of total (%)

US 12,012 +29.0 38Europe 8,609 +470.9 27Rest of world 1,338 ±0.0 4Antiretrovirals 3,338 +51.5 11Formulations 25,297 +76.2 80

Active Ingredients 6,744 -9.4 21

Eliminations/Others -379 – -1

Aurobindo 31,662 +47.9 100

Figure 1: Breakdown by business segment of Aurobindo Pharma’s sales in itsfinancial third quarter ended 31 December 2014 (Source – Aurobindo)

STADA ARZNEIMITTEL said impairment charges of just overC100 million (US$113 million) related to its businesses in theCommonwealth of Independent States (CIS) and Eastern Europealmost halved its 2014 net profit to C64.6 million, according topreliminary annual results. Currency effects added a further C20.7million burden. The German group expects to report annual groupturnover ahead by 3% to C2.06 billion, equivalent to a 1% rise onceadjusted for acquisitions and currency shifts. And this year, Stadaanticipates lower profits from Russia due to devaluation of the roubleand “increased risks in connection with consumer mood”. G

IN BRIEF

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COMPANY NEWS


US Formulations turnover that increased by 41.8%, coupled withsales growth of more than a fifth in its Emerging Markets

region, helped Zydus Cadila to report group sales ahead by 17.4%to Rs22.0 billion (US$353 million) in its financial third quarterended 31 December 2014.

With sales of Rs8.96 billion, US Formulations accounted forjust over two-fifths of the Indian group’s turnover, while EmergingMarkets added 5% with Rs1.01 billion. During the quarter, thecompany filed five abbreviated new drug applications (ANDAs),taking its total US submissions to 255.

Meanwhile, in India – where Zydus recently became “the firstcompany anywhere in the world” to launch biosimilar adalimumabafter introducing its Exemptia rival to AbbVie’s Humira blockbuster(Generics bulletin, 16 January 2015, page 17) – sales rose bymore than a tenth to Rs8.46 billion, comfortably compensating fordouble-digit sales dips in Europe and Latin America to Rs847 millionand Rs610 million respectively (see Figure 1).

Zydus – which halted operations in Japan a year ago (Genericsbulletin, 3 February 2014, page 3) – increased its turnover throughjoint ventures and alliances by a fifth to Rs1.22 billion as activepharmaceutical ingredient (API) sales stalled at Rs734 million.

The group’s pre-tax profit rose by more than half to Rs3.75billion, aided by lower finance costs, as Zydus increased its researchand development investment by 52.7% to Rs1.88 billion. G

Growth in US helpsZydus to advance


Human Health sales rising by almost two-fifths to US$55.4 millionhelped Aceto to increase its group sales by 6.2% to US$124

million in its financial second quarter ended 31 December 2014.Higher selling, general and administrative expenses caused a slightdrop in pre-tax profit to US$10.5 million.

However, chief executive officer Sal Guccione commented,Human Health turnover – which was driven by Aceto’s acquisitionof Pack Pharmaceuticals last year (Generics bulletin, 4 April 2014,

page 3) – had been stung by a US$12.5 million impact from price-protection adjustments associated with increases. “The benefit of [this]should be realised later this fiscal year and in future periods,” he noted.

Those improved Human Health sales marginally overcamePharmaceutical Ingredients and Performance Chemicals dips (seeFigure 1), the former of which Guccione attributed to lower sales ofan undisclosed “high-margin” active pharmaceutical ingredient (API).

While the Aceto head insisted he was confident that Aceto’spipeline of 52 abbreviated new drug applications (ANDAs) – ofwhich 24 had been pending US Food and Drug Administration (FDA)approval for more than two years – would further drive sales, heacknowledged the industry was “seeing slowness” in FDA approvals.Potential launches this year include paricalcitol soft-gel capsulesbought from Par last year as part of a US$8.2 million deal (Genericsbulletin, 19 September 2014, page 17). G

Pack pushes Acetoto single-digit rise

SECOND-QUARTER RESULTS


India 8,464 +10.5 39

US 8,959 +41.8 41Europe 847 -28.6 4Latin America 610 -11.3 3Emerging Markets 1,013 +22.5 5APIs 734 +0.4 3Animal Health/others 136 -16.5 1Exports 12,298 +22.3 56

Joint ventures 1,217 +20.2 6

Zydus Cadila 21,979 +17.4 100

Figure 1: Breakdown by business and region of Zydus Cadila’s gross sales in itsfinancial third quarter ended 31 December 2014 (Source – Zydus Cadila)

Business Second-quarter sales Change Grosssegment (US$ millions) (%) margin (%)

Human Health 55.4 +39.2 29.5

Performance Chemicals 35.8 -8.8 18.9

Pharmaceutical Ingredients 32.6 -13.1 21.3

Aceto 123.8 +6.2 24.3

Figure 1: Breakdown by business segment of Aceto’s sales and gross margin inthe financial second quarter ended 31 December 2014 (Source – Aceto)

Fresenius Kabi has divested its German intravenous oncologycompounding business, CFL, for an undisclosed sum. The purchaser

is NewCo Pharma, a compounding company founded by pharmacistMichael Schill.

Despite having sold Oberursel-based CFL, which generated aturnover of C77 million (US$88 million) last year through a networkof centres spread through Germany, Kabi plans to remain active inthe compounding business. “In Germany,” the firm stated, “the focuswill be on parenteral nutrition products, an area that offers attractivegrowth opportunities.” G

DIVESTMENTS

Kabi divests its compounder

Russia’s Biocad plans to invest more than RUB3.0 billion (US$48million) into constructing a raw-materials plant for monoclonal

antibodies next to its existing operations in Saint Petersburg, Russia.The company has started designing the project and expects commercialproduction to begin by 2018.

According to the company’s founder and chief executive, DmitriyMorozov, the facility will help to meet “unforeseen demand” for thefirm’s monoclonal antibodies, especially for rituximab, for whichBiocad won a supply contract worth of RUB5.98 billion in a recentRussian government tender (Generics bulletin, 3 November 2014,page 19). He said the new plant would mainly produce oncologyand autoimmune monoclonal antibodies.

Meanwhile, last year, Biocad almost trebled its turnover toRUB8.5 billion. With three upcoming oncology launches – includingbortezomib, bevacizumab and empegfilgrastim (Generics bulletin,16 January 2015, page 22) – the Russian company expects to raiseits turnover by 30% to around RUB11.0 billion this year. G

MANUFACTURING/ANNUAL RESULTS

Biocad plans monoclonal site

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COMPANY NEWS


Arecovery in its Brazilian business enabled Sanofi’s Generics unitto report sales that increased by 11.1% as reported, and by 16.2%

at constant exchange rates, to C1.81 billion (US$2.06 billion) last year.Excluding Brazil, the unit suffered a 2.8% constant-currency decline.

Including Brazil, Generics sales in Emerging Markets advancedby 38.8% on a constant-currency basis to C1.11 billion. That gainmore than outweighed sales slides of 4.3% to C533 in Western Europeand 31.3% to C123 million in the US, as Generics turnover in Sanofi’sRest of the World region climbed by 27.8% to C43 million.

The Generics unit’s “very satisfactory recovery in Brazil” cameagainst a 2013 performance in which “challenges in Brazil” – resultingfrom loading trade channels with “significantly and inappropriatelyin excess of volumes needed to satisfy sell-out demand” – causedglobal Generics turnover to fall by 11.9% to C1.63 billion (Genericsbulletin, 14 February 2014, page 2).

Brazilian turnover up by 22% to C71 million in the fourthquarter of last year contributed to a 4.5% constant-currency Genericsgain in Emerging Markets to C291 million. But Sanofi’s total fourth-quarter sales of Generics fell by 0.6% – and by 2.3% as reported –to C467 million, reflecting declines of 7.7% to C133 million inWestern Europe and of 25.7% to C29 million in the US. The Restof the World region added C14 million.

Overall annual group sales in Brazil that rose by just over athird – or by 6.9% excluding generics – to C1.38 billion contributedto Sanofi’s total Emerging Markets turnover up 9.3% at constantexchange rates to C11.3 billion. “New initiatives are underway tofurther expand our footprint in these markets,” stated chairman andinterim chief executive officer Serge Weinberg, pledging to “dedicateadditional resources to leverage our leadership position”. EmergingMarkets made up a third of group turnover that rose by 2.5% asreported, and by 4.9% in constant currencies, to C33.8 billion. G

Brazil bounces forGenerics at Sanofi

ANNUAL RESULTS

Lannett remains interested in globalising through acquisitions,and is focused on opportunities in Western Europe, according to

chief executive officer Arthur Bedrosian.Speaking to investors as Lannett reported sales ahead by 70.5%

to US$115 million in its financial second quarter ended 31 December2014, Bedrosian revealed that Lannett had conducted due-diligenceevaluations of two companies, one of which was an “attractive company”that would be a “good candidate” for a tax-favourable inversion move.

But ultimately, Bedrosian insisted, an accretive transaction wasLannett’s priority as the company sought to close its first transaction.

Lannett recently enlisted the global expertise and acquisitionsexperience of Teva’s Americas Technical Operations head, MichaelBogda, appointing him as company president in lieu of Bedrosian(Generics bulletin, 16 January 2015, page 30).

Investors did not quiz Bedrosian on the federal investigationsurrounding Lannett in relation to the company’s pricing practices,for which it was recently served with a grand jury subpoena seekingcorporate documents (Generics bulletin, 16 January 2015, page 4).

As Figure 1 shows, those price increases caused sales in severalof Lannett’s therapeutic categories to soar ahead, including a nearfifteen-fold increase in turnover from the company’s gallstonetreatments, while the US firm’s biggest sellers – its thyroid-deficiencytreatments such as levothyroxine – rose by 69.7% to US$44.5 million.

In total, price increases added US$50.9 million to Lannett’s sales,comfortably outstripping a US$3.4 million hit from reduced volumes.

During its financial second quarter, the US firm received finalapproval for a generic version of Oak Pharmaceuticals’ Cosopt(dorzolamide/timolol) 2%/0.5% ophthalmic solution (Genericsbulletin, 16 January 2015, page 20), although Bedrosian concededthat sales were expected to be “modest” as Lannett was a late entrant tomarket. The US firm currently has 20 abbreviated new drug applications(ANDAs) pending US approval, five of which contain paragraph IVpatent challenges, including generic Thalomid (thalidomide) that isthe subject of litigation versus Celgene.

With research and development and other operating expensesonly slightly higher than in the prior-year quarter, Lannett’soperating profit soared by 162% to US$66.5 million. G

Lannett turns gazeto Western Europe

BUSINESS STRATEGY/SECOND-QUARTER RESULTS

Privately-owned Polpharma has told Generics bulletin that its activepharmaceutical ingredient (API) manufacturing facilities in January

this year passed a US Food and Drug Administration (FDA) inspectionwith no Form 483 observations. The Polish firm noted that this wasthe fourth time in 11 years the FDA had reported no manufacturingdeficiencies at its API plants, following previous inspections in2004, 2009 and 2012.

The group – which claims to be “among the top-20 generic drugmanufacturers in the world, and a significant European producer ofAPIs” – has seven manufacturing plants and six research anddevelopment centres in Poland, Russia and Kazakhstan.

Polpharma’s Chimfarm subsidiary in Kazakhstan has just openedan injectables unit at its facility in Shymkent as part of thecompany’s “major investment project” aimed at expanding its productioncapacities. The unit – which should produce over 100 million ampoulesin its first year of production – has an annual capacity of filling 300million injectable ampoules, 2 million bags and 2 million vials.

Chimfarm – which is investing around US$100 million in theproject – has also started modernising its production lines for solid-doseforms and antibiotic powder filling. G

FDA okays Polpharma plantsMANUFACTURING

Second-quarter sales Change Proportion(US$ millions) (%) of total (%)

Thyroid deficiency 44.5 +69.7 39

Cardiovascular 18.3 +8.3 16

Gallstone 16.7 +1372.7 15

Pain management 7.6 +11.4 7

Migraine 6.9 +195.4 6

Glaucoma 5.5 +272.2 5

Antibiotic 3.3 -22.8 3

Gout 3.0 +48.8 3

Obesity 1.0 +12.9 1

Other 7.9 +52.0 7

Lannett 114.8 +70.5 100

Figure 1: Breakdown by therapeutic category of Lannett’s sales in its financialsecond quarter ended 31 December 2014 (Source – Lannett)

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COMPANY NEWS


Double-digit sales declines in Russia and Ukraine caused GedeonRichter’s Pharmaceutical turnover to decline by 3.9% to C988

million (US$1.13 billion) last year. Including the Hungarian group’sloss-making Wholesale and Retail business, which operates mainlyin Romania, group turnover fell by 3.4% to C1.15 billion.

Pharmaceutical sales in Russia tumbled by 18.6% to C274million, although the local-currency slide was a more modest 3.7%.

While wholesaler destocking had depleted local turnover, Richterenjoyed “good sales performances” from oral contraceptives, Diroton(lisinopril), Mydocalm (tolperisone), and Panangin (asparaginates).

The firm blamed “more strict receivables control and voluntaryshipment restrictions” amid the local political and economic upheavalfor its turnover in Ukraine plummeting by 23.0% to C55.0 million.That fall was offset in part by sales in other Commonwealth of

Independent States (CIS) members rising by 9.0% to C78.5 million.Total sales in the region fell by 15.1% to C407 million (see Figure 1).

Pharmaceutical turnover in the European Union (EU), excludingHungary, advanced by 2.5% to C321 million. This came despite a13.5% drop to C64.1 million in Poland amid wholesaler destockingand a mild flu season hitting sales of Groprinosin (inosine pranobex).

Sales in Romania fell by 11.1% to C28.8 million even after thefourth-quarter introduction of Coltowan (ezetimibe), while turnoverin the Czech Republic was 8.8% lower at C24.8 million.

In Western Europe, stronger sales of Esmya (ulipristal acetate)helped to push up Pharmaceutical turnover by 2.9% to C66.5 millionin Germany, by around two-fifths to C18.0 million in France, andby about 70% to C13.9 million in the UK. Spanish sales doubled toC14.8 million on the “good performance of Esmya”.

The Hungarian group said its reported 1.3% sales rise to C104million in its domestic market equated to a local-currency advanceof 5.4% as the firm launched Ossica (ibandronate), Panagin Forte(asparaginates) and zoledronic acid towards the end of last year.

In the US, turnover increased by 9.5% to C52.1 million “froma low base” on higher sales of finished-dose finasteride and the PlanB One Step (levonorgestrel) emergency contraceptive.

Lower gross margins and a lack of milestone payments cut thegroup’s operating profit by 18.9% to C127 million. G

Russia and Ukrainehit Richter’s results

ANNUAL RESULTS

Annual sales Change Proportion(CC millions) (%) of total (%)

Russia/CIS 407.3 -15.1 36European Union* 321.2 +2.5 28Hungary 103.5 +1.3 10US 52.1 +9.5 4China 44.1 +25.6 4Latin America 18.8 +66.4 2Rest of World 41.4 +5.3 4Pharmaceutical 988.4 -3.9 86

Wholesale & Retail 179.5 -0.5 16

Eliminations/Other -22.2 – -2

Gedeon Richter 1,145.7 -3.4 100

* excluding Hungary

Figure 1: Breakdown of Gedeon Richter’s sales in 2014 (Source – Gedeon Richter)

PAR PHARMACEUTICAL expects to record a turnover of US$1.31billion for 2014. Generic Entocort EC (budesonide) should contributeUS$143 million to that total, with rivals to Wellbutrin XL (bupropion)and Rythmol SR (propafenone) adding US$84 million and US$76million respectively. Sales of generic versions of Kapvay (clonidine),Lamictal XR (lamotrigine) and Toprol XL (metoprolol) are eachset to top US$40 million, according to preliminary figures. TheUS generics specialist anticipates 2014 research and developmentspending of US$116 million, with a gross profit of US$474 millionand earnings before interest, tax, depreciation and amortisation(EBITDA) of US$183 million.

PHARMASYNTEZ – which claims to be the Russia’s largestmanufacturer of tuberculosis drugs – is acquiring a productionplant located in Tyumen, Russia, from local firm YugraFarm toproduce its domestic infusion solutions, as well as hormone therapies.The Russian company intends to invest RUB1.7 billion (US$27million) over the next two years in modernising the facility, whichits says will comply with international good manufacturing practice(GMP) standards and employ 250 staff.

CO-OPERATIVE PHARMACY – the UK’s third-largest pharmacychain with 780 stores – is to be renamed as Well following itstakeover by Bestway Group in a £620 million (US$955 million)deal last year (Generics bulletin, 8 August 2014, page 10). Bestwayplans to invest £200 million over the next five years in expandingthe business, with the goal of lifting the chain’s annual turnoverfrom £750 million to £1.0 billion by 2019.

DIVI’S LABORATORIES intends to invest around Rs5.0 billion(US$81.0 million) in setting up a third manufacturing facility inIndia. The Indian bulk-drugs producer has asked the regionalgovernment of Andhra Pradesh to allot land near Kakinada. In itsfinancial third quarter ended 31 December 2014, Divi’s increasedits turnover by 15% to Rs7.91 billion, but its pre-tax profit edgedup by just 2% to Rs2.78 billion.

AMNEAL has appointed GE Capital to act as its agent for a US$250million loan. “The proceeds from this financing will be used tofund capital expansion related to manufacturing and a distributionto existing shareholders,” GE Capital said.

INDOCO REMEDIES reported net sales ahead by 13% to Rs2.13billion (US$34.2 million) in the three months ended 31 December2014. The Indian firm’s domestic turnover grew by 7% to Rs1.30billion, while its sales outside of India expanded by 23% toRs833 million. Lower finance costs helped Indoco to improve itspre-tax profit by 56% to Rs282 million.

FARMAK said it remained market leader in Ukraine, despite thegroup’s turnover falling by a tenth to US$122 million last year.Citing data from market researcher SMD, the company claimed itranked first by value in Ukraine, ahead of Novartis and Menarini.

JB CHEMICALS & PHARMACEUTICALS increased its net salesby a tenth to Rs2.57 billion (US$41.3 million) in its financial thirdquarter ended 31 December 2014. That growth was aided by startingsales and distribution activities in Russia and the Commonwealthof Independent States (CIS) last year through a wholly-ownedsubsidiary. Indian formulations sales increased by 11% to Rs950million, while formulations exports grew by 9% to Rs1.29 billion.But active pharmaceutical ingredient (API) turnover slippedslightly to Rs258 million. G

IN BRIEF

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Podravka is building a 23,000 sq m solid-dose, semi-solids andliquids facility in Croatia to ease capacity constraints and develop

value-added generics such as effervescent tablets, sprays, patches andmedicated chewing gum. The Croatian firm said its utilisation ofits current granulation and compression capacity was at 89%, whilesemi-solids and liquids lines were working on Saturdays. Constructionof the C51.4 million (US$58.5 million) project – including a governmentincentive worth up to C20.0 million – is due to start in March, witha manufacturing licence targetted by the end of March 2017.

Podravka’s Pharmaceuticals turnover fell by 1.3% to CrK840million (US$124 million) last year, equivalent to a 1.9% increase atconstant exchange rates.

In its home market, an estimated CrK57.2 million hit from fromreimbursement cuts imposed by the Croatian Health Insurance Fundin May 2013 and February 2014 wiped out 7.0% volume growth assales fell by 10.4% to CrK396 million despite launches via its Belupounit including Eminens SR (ropinirole) sustained-release tablets andViner Mint (sildenafil) chewable tablets.

Gains in Bosnia & Herzegovina contributed to double-digit growthto CrK225 million in the firm’s South-East Europe region. But a 16.1%constant-currency rise in Eastern Europe became a reported 1.6% dropto CrK162 million due to the devaluation of the Russian rouble.

Growth of more than a third to CrK49.5 million in CentralEurope came from dermatology products, entering the Polish marketand high single-digit growth in the Czech Republic.

Pharmaceuticals sales accounted for just under a quarter of theCroatian food and beverages group’s turnover that fell by 3.4% toCrK3.50 billion. But a Pharma operating profit down by 31.6% toCrK80.2 million was still more than half of the group total. G

COMPANY NEWS


Increased demand for its active pharmaceutical ingredient (API)contract-manufacturing services has led Cambrex to begin expansion

work at its US production facility in Charles City, Iowa.Noting that this was the second such expansion in less than three

years at its Charles City complex, the US company said it expectedto invest US$45-US$50 million building an additional current goodmanufacturing practice (cGMP) production unit and related infrastructurealongside existing operations.

Slated for completion early next year, the new plant, which willbe capable of handling potent APIs, will allow Cambrex to “quicklyand efficiently further expand cGMP capacity, as future growthrequires”. It will add 70 cubic metres of reactor capacity as well as4,200 sq m of warehouse space. Expansion work has also begun at theUS firm’s sites in Karlskoga, Sweden, and Milan, Italy, revealed StevenKlosk, Cambrex’ president and chief executive officer.

Last year, strong demand for its exclusive and controlled-substanceproducts pushed Cambrex’ group turnover ahead by 17.7% to US$375million. But increased research and development spending and apension-settlement charge lowered the US firm’s operating marginby 1.6 percentage points to 14.0%. Cambrex is forecasting salesgrowth of 16-20% this year. G

Cambrex is growingIowa bulk-drugs site

MANUFACTURING/ANNUAL RESULTS

Podravka invests in plantMANUFACTURING/ANNUAL RESULTS

Recent launches such an authorised generic of Astellas’ Protopic(tacrolimus) 0.03% and 0.1% ointments and “increased volumes”

pushed up Perrigo’s Prescription Pharmaceuticals sales by 12% toUS$277 million in the US firm’s financial second quarter ended 27December 2014. The Prescription business accounted for over a quarterof group turnover that advanced by 9% to US$1.07 billion, largely dueto US$54 million of new-product sales and a US$79 million increasein royalties from Biogen Idec’s sales of Tysabri (natalizumab).

Double-digit Prescription sales growth helped to offset lowerConsumer Healthcare and Nutritionals sales, while turnover fromPerrigo’s Active Pharmaceutical Ingredient (API) segment stalledat US$30.0 million (see Figure 1).

The Protopic authorised generic launch (Generics bulletin, 5December 2014, page 27) contributed to the Prescription segmentgenerating US$33 million of sales from new products. Those gainscomfortably offset a US$14 million hit from discontinuing products.

Having also introduced a US rival to Mallinckrodt’s Pennsaid(diclofenac sodium) 1.5% topical solution in December last year, Perrigoin January introduced an alternative to AbbVie’s Androgel (testosterone)1.0% gel and a rival to Galderma’s Clobex (clobetasol propionate) 0.05%spray with 180-day generic market exclusivity (Generics bulletin,6 February 2015, page 20). And the firm has just received US Food andDrug Administration (FDA) approval for the first generic of Novartis’Transderm Scop (scopolamine) extended-release transdermal film.

The Prescription segment improved its second-quarter grossmargin by 1.8 percentage points to 54.0%, but “higher investmentsin both clinical research and development and in growing the specialtypharmaceuticals salesforce” following a deal for Lumara’s women’shealth portfolio contributed to its operating margin dipping by justover a point to 39.6%. Perrigo’s group operating margin improved bymore than eight percentage points to 17.2% following prior-year chargeslinked to acquiring Elan and Tysabri.

In its current financial year ending in June 2015, Perrigo expectsto generate at least US$235 million from sales of newly-launchedproducts. Among the firm’s pipeline is an OTC store-brand versionof Sanofi’s Nasacort Allergy 24HR (triamcinolone) nasal spray thatit plans to launch through a tie-up with Teva in time for the next USallergy season. Perrigo is also pushing into gummy vitamins througha recently struck alliance with Ferrara Candy.

By the end of March, Perrigo expects to close a C3.6 billion(US$4.1 billion) deal for Belgium’s Omega Pharma that it agreed inNovember last year (Generics bulletin, 14 November 2014, page 3). G

Protopic rival pepsPerrigo’s turnover

SECOND-QUARTER RESULTS

Business Second-quarter sales Change Operatingsegment (US$ millions) (%) margin (%)

Consumer Healthcare 530 -1 14.1Prescription Pharma 277 +12 39.6Nutritionals 131 -7 5.5Specialty Sciences 87 +1.070 11.0API 30 ±0 24.7Other 18 -4 6.4

Perrigo 1,072 +9 17.2*

* includes US$25.4 million of unallocated expenses

Figure 1: Breakdown by business segment of Perrigo’s sales and operating marginin its financial second quarter ended 27 December 2014 (Source – Perrigo)

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COMPANY NEWS


Lupin overcame delays in obtaining regulatory approvals to postgroup turnover ahead by 5% to Rs31.4 billion (US$506 million)

in its financial third quarter ended 31 December 2014. Double-digitadvances in Europe and India pushed up Formulations sales by 7%to Rs28.7 billion, more than countering a 7% slide to Rs2.76 billionin active pharmaceutical ingredient (API) turnover on steep declinesin the US and Europe.

Lower raw-material costs and a 4% reduction in research anddevelopment spending helped to boost the debt-free Indian group’spre-tax profit by 16% to Rs8.53 billion.

“The company’s continued focus on improving operationalefficiencies has led to sustained margins and profit growth,notwithstanding regulatory delays that have resulted in pressureson the top line,” remarked managing director Nilesh Gupta.

Three abbreviated new drug application (ANDA) submissionsand three approvals during the quarter left approved just over half– 108 – of the 203 ANDAs the firm has filed with the US Food and

Drug Administration (FDA). The Indian company believes it has todate made 30 first-to-file opportunities – targeting US$13.7 billionin annual brand sales – of which half are exclusive opportunities.

Pointing out that it had received “no [Form] 483 observationsin the past five FDA audits”, Lupin said it was market leader for 30of the 74 US generics it marketed as of 31 December 2014. Eight USproduct launches since April 2014 helped to lift US Formulationssales by 4% to Rs14.0 billion, equivalent to a 1% local-currency rise.

European turnover climbed by 15% to Rs805 million as Lupin“saw robust growth across all businesses”. The Indian group achieveda 14% sales rise to Rs7.44 billion in its domestic market throughgrowth in chronic conditions.

In Japan – where Lupin claims to be the eighth-largest genericsplayer – turnover fell by 8% to Rs3.42 billion as reported, but increasedby 4% in local-currency terms. The Kyowa solid-dose businessregistered a 9% turnover rise on “good matured-products growth”, butthe Irom subsidiary’s sales slipped by 1% as the injectables specialistundertook “cost-rationalisation initiatives to enhance profitability”.

Adverse currency shifts halved the 19% local-currency growthproduced by Lupin’s Pharma Dynamics affiliate in South Africa to areported 9% turnover gain to Rs1.07 billion. Formulations sales up bymore than a third to Rs1.91 billion in the Rest of the World regionincluded the first full quarter after Lupin bought Mexican ophthalmicsfirm Laboratorios Grin (Generics bulletin, 4 April 2014, page 3). G

Lupin grows despiteregulatory hold-ups



US 14,043 +4 45India 7,438 +14 24Japan 3,422 -8 11South Africa 1,070 +9 3Europe 805 +15 2Rest of World 1,913 +35 6Formulations 28,691 +7 91

APIs 2,758 -7 9

Lupin 31,449 +5 100

Figure 1: Breakdown by region and business of Lupin’s sales in its financial thirdquarter ended 31 December 2014 (Source – Lupin)

Cutting manufacturing costs helped Japan’s Towa to improve itsprofit margins in the first nine months of its financial year ending

31 March 2015, despite price cuts mandated by the country’s NationalHealth Insurance (NHI) system.

As Towa’s sales for the period rose by 17.3% to ¥53.1 billion(US$443 million), the firm’s costs of goods rose by 15.5% to ¥25.8billion, while selling, general and administrative expenses increasedby just 12.9% to ¥18.7 billion. This gave Towa an operating profit34.8% higher at ¥8.61 billion, and an operating margin that jumpedby 2.1 percentage points to 16.2%.

Improved profitability came despite a 17.8% increase in researchand development costs to ¥4.66 billion – of a forecasted total of¥6.5 billion for the full financial year – as a result of Towa investingin its development pipeline. Products launched in 2014, includingorodispersible valsartan, contributed ¥1.4 billion to sales, whilethose introduced in 2013 – such as orodispersible pitavastatin –accounted for ¥3.7 billion, or around 7% of sales.

In light of the latest figures, Towa has revised its full-year forecastto reflect its improved profitability. The firm expects to generate anoperating profit of ¥10.0 billion – compared to its previous estimateof ¥7.80 billion – on projected full-year sales that remain unchangedat ¥72.0 billion. This will give Towa an operating margin of 13.9%,rather than the 10.8% originally forecast. G

Towa cuts its coststo improve margins

NINE-MONTH RESULTS

Orion says its generics are now “accounting for a greater proportionof total sales” as several of its brands come under generic

competition. The Finnish group reported a 0.8% increase in groupturnover to C1.02 billion (US$1.15 billion) last year.

“Competition in Finland, the most important generics market forOrion, remains intense in 2015. However, product launches continueto support Orion’s position as market leader,” the firm stated.

Last year, sales by Orion’s Specialty Products off-patent, generics,OTC and biosimilars division increased by 11% to C427 million. Thatrise was driven in part by sales of generic entacapone more than doublingto C26 million, as the rest of the division’s portfolio showed 7% growth.

In Finland, the division posted a 9% sales increase to C256 million,while in Scandinavia turnover advanced by 21% to C50 million. Butthe depreciation of the Russian rouble caused sales in Eastern Europeand Russia to stall at C56 million.

Infliximab sales reached C6 millionOrion said the division had derived sales of C6 million from

marketing the Remsima (infliximab) biosimilar in Finland, Scandinaviaand the Baltic States through an agreement with South Korea’sCelltrion. In Norway, Orion is offering discounts of up to 72%compared to the reference brand, Remicade (see page 29).

Weaker sales of a key product reduced by a tenth to C57 millionturnover by Orion’s Fermion active pharmaceutical ingredients (APIs)division. Proprietary Products sales fell by 4.4% to C373 million, duein part to generic competition to Stalevo (carbidopa/levodopa/entacapone) in Germany, while Animal Health, Diagnostics andother operations contributed C158 million. G

ANNUAL RESULTS

Off-patent drugs assist Orion

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COMPANY NEWS


The US Food and Drug Administration (FDA) has rescinded awarning letter that the agency issued in 2012 against a Hameln

Pharma sterile injectables facility in Germany that has just beenacquired by Swiss group Siegfried.

In a brief close-out letter, the agency said corrective actionsundertaken at the factory in Hamelin, Germany, appeared to haveaddressed the violations listed in the warning letter from December2012. That letter – which resulted from an inspection conducted in June2012 – highlighted issues with staff training and systems for monitoringenvironmental conditions (Generics bulletin, 1 February 2013, page 6).

“Following revocation of the warning letter, the path has beencleared for the Hameln Pharma facility to be immediately and fullyintegrated into Siegfried’s worldwide compliance system,” statedthe Swiss group, which bought the German injectables contractmanufacturer towards the end of last year (Generics bulletin, 5December 2014, page 1).

German authorities cleared facilityPointing out that one of its US customers could now resume imports

of products made at the Hameln site, Siegfried said German regulatoryauthorities had recently renewed Hameln’s good manufacturingpractice (GMP) certificate.

At the time the SFr60 million (US$63 million) deal for Hamelnwas announced, a spokesperson for Siegfried told Generics bulletinthe Swiss firm was confident that the FDA would soon lift the warningletter following a recent re-inspection. G

Siegfried sorts outFDA Hameln letter

MANUFACTURING

Quadrupling sales of its bulk and finished-dose oxycodone helpedMallinckrodt to increase its Specialty Generics turnover by 13.7%

to US$284 million in the US firm’s financial first quarter ended 26December 2014. Of that total, US$234 million was generated in theUS, US$23.7 million in Europe, the Middle East and Africa (EMEA),and US$26.7 million in other markets.

The oxycodone gains following “strategic pricing initiatives”more than made up for the blow of Mallinckrodt’s rivals to Janssen’sConcerta (methylphenidate) extended-release tablets – along withKudco’s generic versions – losing their AB-rating for therapeuticequivalence to the brand last year (Generics bulletin, 5 December2014, page 23). The firm’s methylphenidate sales fell by 13.7% toUS$48.6 million (see Figure 1).

Mark Trudeau, Mallinckrodt’s president and chief executiveofficer, said the firm planned to keep methylphenidate on the marketas a BX-rated product – indicating insufficient data to determinetherapeutic equivalence – for the “foreseeable future”. “Clearly, as aBX-rated product, it’s going to be at a lower revenue rate [in 2015]than it was in 2014,” Trudeau commented, reiterating that Mallinckrodtbelieved “very strongly” that the product was safe and effective.

The company had acted quickly to launch a line of hydrocodoneSchedule II combination products following reclassification of thecontrolled substance, he pointed out.

Meanwhile, Trudeau said that Mallinckrodt was “aggressivelypursuing” a number of acquisitions, based on the firm’s strong cashflow and operational capability.

The bulk of Mallinckrodt’s 60.4% group turnover rise to US$866million came from Specialty Brands sales rising by more than sixtimes to US$374 million as the US firm added US$338 million throughincorporating the Ofirmev (acetaminophen) and Acthar (corticotropin)injectables that it purchased in March and August last year respectively.

This dwarfed a turnover slide of almost a tenth to US$199million in Mallinckrodt’s Medical Imaging segment, which the USfirm attributed to restructuring initiatives and adverse exchange rates.

Even with a US$126 million intangible amortisation charge linkedlargely to the Acthar deal, Mallinckrodt’s operating profit jumped by74.3% to US$127 million. Oxycodone pushed up the Specialty Genericssegment’s operating margin by almost a percentage point to 49.4%. G

Oxycodone bulks upMallinckrodt’s sales

FIRST-QUARTER RESULTS

First-quarter sales Change Operating(US$ millions) (%) margin (%)

Specialty Brands 373.6 +526.8 39.7

Methylphenidate ER 48.6 -13.7 –

Oxycodone 47.0 +305.2 –

Hydrocodone 34.0 +13.0 –

Other controlled substances 111.9 -6.9 –

Other generics 42.7 +34.7 –

Specialty Generics 284.2 +13.7 49.4

Medical Imaging 199.3 -8.8 8.7

Other 9.2 -24.0 –

Mallinckrodt 866.3 +60.4 14.7*

* includes US$179 million of unallocated corporate expenses

Figure 1: Breakdown of Mallinckrodt’s sales in its financial first quarter ended26 December 2014 (Source – Mallinckrodt)

Patent settlement agreements reached by Impax for three US brands –Shire’s Adderall XR (amphetamine salts), Endo’s Opana ER

(oxymorphone) and Pfizer’s Effexor XR (venlafaxine) – are beinginvestigated by Alaska’s attorney-general to determine whether theyviolated state law by unlawfully delaying generic entry in Alaska.

The US firm said it intended to cooperate with the investigation,and would produce documents and information in response to thecivil investigative demands it had received for each product. “To theknowledge of the company,” commented Impax, “no proceedingshave been initiated at this time.” G

INVESTIGATIONS

Impax investigated for delays

A12% increase in Indian Formulations sales was largely responsiblefor Alembic Pharmaceuticals increasing its turnover by 6% to

Rs5.15 billion (US$82.8 million) in its financial third quarter ended31 December 2014.

With sales of Rs2.83 billion, Indian Formulations accounted for55% of the group total as International Formulations turnover fell by4% to Rs1.47 billion. Active pharmaceutical ingredient (API) sales roseby 7% to Rs813 million, while export incentives added Rs36.5 million.The group’s pre-tax profit edged up by 1% to Rs900 million. G


Alembic advances in India

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COMPANY NEWS


Double-digit sales growth in India and Europe, coupled withturnover in Latin America more than doubling, helped Glenmark

overcome a sales tumble of almost a third in its Rest of the Worldbusiness as the Indian company’s group turnover increased by 6.2%to Rs17.0 billion (US$273 million) in its financial third quarterended 31 December 2014.

But a ramp up in material costs and purchase of stock-in-tradecaused Glenmark’s pre-tax profit to tumble by 31.4% to Rs1.51 billion.

In the firm’s Rest of the World segment, sales fell by 31.3% toRs2.07 billion, due in part to currency depreciation throughout thebusiness. However, Glenn Saldanha, the Indian firm’s chairman andmanaging director, revealed that the company had been boosted inRussia by a recent approval for generic Seretide (fluticasone/salmeterol),and was also anticipating a further “two or three large approvals”.

“We have a positive view of Russia, it is very profitable and ourrespiratory portfolio is doing very well,” Saldanha told investors, addingthat the company would not look to capitalise in the country with priceincreases and would instead adopt a “wait and watch approach”.

As Figure 1 shows, Glenmark’s sales in the US slid by 2.7% toRs5.07 billion. Saldanha blamed a slowdown in US generic approvals– evidenced by Glenmark receiving just one US Food and DrugAdministration (FDA) approval during the quarter, for rivals toAstraZeneca’s Prilosec (omeprazole) 10mg, 20mg and 40mg delayed-release capsules – and channel consolidation for that turnover fall.

But, Saldanha insisted, the company’s fortunes in the US wouldturn as product approvals accelerated, beginning in Glenmark’s current

financial quarter. The firm also had “a couple of sure launches”,including generic desmopressin, according to Glenmark’s US head,Robert Matsuk.

The Indian firm’s domestic sales rose by 13.6% to Rs4.33 billion,as Glenmark improved its market share for cardiovascular andrespiratory disease treatments, anti-infectives and diabetes drugs.However, these gains were partially offset by losing share forgynaecology and dermatology drugs.

Elsewhere, Latin American sales continued to soar, more thandoubling to Rs2.34 billion, thanks to surges in Mexico and Venezuela.“We’ve launched a respiratory product in Brazil, but still continue tostruggle for product approvals in the country,” Glenmark revealed.

Meanwhile, despite sales growing by more than a quarter toRs1.73 billion in Europe, Glenmark said it had struggled in Romaniadue to the “challenging business environment”. However, this wascomfortably offset by strong growth in the UK, Germany and Poland. G

Glenmark grows itssales as profits slide


Region Third-quarter sales Change Proportion(Rs millions) (%) of total (%)

US 5,072 -2.7 30India 4,331 +13.6 25Latin America 2,344 +105.8 14Rest of world 2,071 -31.3 12Europe 1,730 +27.3 10APIs 1,465 -1.0 9

Glenmark 17,013 +6.2 100

Figure 1: Breakdown by business segment and region of Glenmark Pharmaceuticals’sales in its financial third quarter ended 31 December 2014 (Source – Glenmark)

DSM said “solid growth and operational improvements at its Yushu,China, intermediates plant” helped to push up turnover by its DSMSinochem affiliate by 8% to C399 million (US$452 million) last year.

LUPIN said its manufacturing facility at Pithampur near Indore,India, had received six ‘Form 483’ observations following anaudit by the US Food and Drug Administration (FDA) in Januarythis year. “Since then, the Indore facility has received oneabbreviated new drug application (ANDA) approval and two site-transfer approvals,” the Indian group noted, adding that its LBCbioresearch centre in Pune, India, had passed an FDA inspectionwithout any observations. Lupin has just secured US approval forbimatoprost 0.03% ophthalmic solution from the Indore facility.

NATCO PHARMA reported consolidated turnover down by 4%to Rs1.95 billion (US$31.4 million) in its financial third quarterended 31 December 2014. An exceptional charge of Rs151 millionfor settling a legal case contributed to the Indian firm’s pre-taxprofit halving to Rs191 million.

JEAN COUTU said sales by its Pro Doc generics operation advancedby 6% to C$50.7 million (US$42.0 million) in its financial thirdquarter ended 29 November 2014. The Pro Doc rise helped to pushup the Canadian retailing group’s turnover by 3% to C$737 million.

DISHMAN said a three-day inspection by the US Food and DrugAdministration (FDA) – initially planned to last five days – confirmedthat its site in Veenendaal, the Netherlands, complied with currentgood manufacturing practice (cGMP) standards. The plantspecialises in making vitamin D analogues. Three-quarters of theIndian group’s turnover that moved ahead ahead by 23% to Rs3.86billion (US$62.0 million) in the three months ended 31 December2014 came from contract research and manufacturing services,with the other quarter derived from other activities such as salesof bulk drugs and intermediates.

STRIDES ARCOLAB reported sales that stalled at Rs3.26billion (US$52.5 million) in its financial third quarter ended 31December 2014, during which it filed four products with the USFood and Drug Administration (FDA) and received approval forcalcitriol soft-gel capsules. The Indian firm’s Institutional businessaccounted for Rs1.28 billion of that total, emerging marketsRs1.01 billion and regulated markets Rs966 million.

VERTEX has completed construction of a manufacturing facilityin Saint Petersburg, Russia, following a RUB1.8 billion (US$27.1million) investment. Intended to comply with international goodmanufacturing practice (GMP) standards, the plant will have anannual capacity of around 70 million packs, covering tablets, capsules,ointments, creams, and sprays. The firm expects to start production,including for contract-manufacturing customers, in the third quarterof this year.

AJANTA PHARMA is qualifying an oral solid-dose facility inDahej, India, and expects to produce regulatory-filing batches withinthe next few months. In its financial third quarter ended 31 December2014, the Indian formulations specialist increased its turnover by21% to Rs3.63 billion (US$58.4 million). Ajanta’s domestic salesrose by 35% to Rs1.32 billion, while its turnover in emerging marketsgrew by 15% to Rs2.23 million, comprising Rs1.10 billion fromAfrica, Rs1.09 billion from Asia and Rs40 million from LatinAmerica. In the US, the firm has 23 abbreviated new drug applications(ANDAs) pending approval. G

IN BRIEF

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MARKET NEWS


Generics manufacturers can now apply to Australia’s Federal Courtto obtain compulsory licences that will allow them to produce

patented drugs for export to developing countries facing health crises.The country’s Intellectual Property Laws Amendment Act 2015 passedby the country’s Senate on 9 February permits the court to determineappropriate remuneration for the patent holder.

A specific section of the amendments dealing with compulsorylicences for patented pharmaceuticals sets out the conditions that mustbe met. The court may order a compulsory licence “if the proposeduse of the pharmaceutical product is to address a public health issuein the eligible importing country”, either in a national emergency or“by the public non-commercial use of the product”.

Noting that such an order may be amended or revoked by the court,the amendments also state that the patentee “must be paid an agreedamount of remuneration, or an amount of remuneration determinedby the court”.

This “adequate remuneration” decided by the court would takeinto account “the economic value to the eligible importing country ofthe use of the patented pharmaceutical invention”.

If the compulsory licensing order is granted on the basis of a“public non-commercial use of the product”, the applicant must firstgive the patentee a notice seeking an authorisation to exploit thepatented invention for non-commercial use. Furthermore, the applicantmust have within 30 days of this notice tried without success to obtainsuch an authorisation “on reasonable terms and conditions”.

Applicants and importing countries must also take “reasonablemeasures” to prevent pharmaceuticals that are exported from Australiaunder such a licence from being used “for a purpose other than thepurpose of addressing the public health problem”.

Separately, the amendments include a broader section oncompulsory licensing in general that allows the Federal Court to granta licence in Australia “if the reasonable requirements of the publicare not being met with respect to a patented invention”.

Despite pharmaceuticals being governed by the separate specificcompulsory licensing measures, the general section notes, this “doesnot prevent a compulsory licence from being ordered under this partin relation to such an invention”. G

Australia can allowcompulsory licensing

INTELLECTUAL PROPERTY

Firms that imported medicines into a European Union (EU) memberstate in which the product enjoyed supplementary protection

certificate (SPC) protection from a country that only became an EUmember state in 2004 – and in which similar SPC protection was notavailable – can rely on the EU’s ‘specific mechanism’ to justify theimport, provided that the SPC holder did not oppose it during themechanism’s one-month waiting period, the Court of Justice of theEU (CJEU) has ruled (Generics bulletin, 3 November 2014, page 14).

The case involved Sigma and Pharma XL importing Merck, Sharpand Dohme’s Singulair (montelukast) from Poland and repackagingit for the UK market in 2010. While an SPC in the UK – whichexpired on 24 February 2014 – existed based on European patentEP0,480,717, similar protection was not available in Poland.

Under the ‘specific mechanism’, patent or SPC holders can givenotification of their intent to oppose parties from importing a productfrom the Czech Republic, Estonia, Latvia, Lithuania, Hungary, Poland,Slovenia or Slovakia into a state where the product is protected. G

Canadian province Quebec expects to save around C$40 million(US$32 million) annually by removing doctors’ ability to mark

prescriptions as non-substitutable, according to provincial healthminister Gaétan Barrette. From 24 April, pharmacists will be ableto substitute a generic even when the prescription is marked “donot substitute”, Barrette announced, although for valid prescriptionsissued before this date the direction not to substitute would behonoured by pharmacists until 1 June.

Exceptions to the rule included ‘class seven’ medicines – a groupof drugs for which treatment needed to be monitored very closely orwhich required very precise dosing – such as immunosuppressants,Barrette explained. Substitution will also still be able to be blocked incases such as patient allergies to inactive ingredients – such as sugarsor colourants – that were present in generics but not in the brand. G

Quebec lifts substitution barREGULATORY AFFAIRS

Further comments on a proposed rule to change requirements forgeneric labelling are being solicited by the US Food and Drug

Administration (FDA) both in writing and at a public meeting.On 27 March, the agency plans to hold a meeting at its White

Oak campus in Maryland to “listen to comments on the proposedrule” – which would require generics firms to update safety informationusing the same ‘changes being effected’ (CBE) process as originators– as well as alternatives to the proposal that was first made in late2013 (Generics bulletin, 15 November 2013, page 1). Attendees mustregister by 20 March, while comments can be made until 27 April.

“Stakeholders may present or comment on the proposed ruleor any alternative proposals intended to improve communication ofimportant newly-acquired drug safety information to healthcareprofessionals and the public,” the FDA said. The meeting comes inresponse to requests from the US Generic Pharmaceutical Association(GPhA) and brand industry association PhRMA.

The GPhA has repeatedly voiced its opposition to the proposedrule, citing concerns that it could lead to multiple labels, causingconfusion. The association last year threatened legal action if the FDAreleased an unchanged final rule as originally scheduled in December(Generics bulletin, 3 October 2014, page 9). The FDA subsequentlydeferred its decision, having received “a great deal of public inputfrom various stakeholders during the comment period” (Genericsbulletin, 5 December 2014, page 15). G

FDA reopens debateon label change rule

REGULATORY AFFAIRS

REGULATORY AFFAIRS

EU clarifies SPC import law

BIO – the US Biotechnology Industry Organization – has claimed thata proposed patent-reform bill would “undermine the ability oflegitimate patent owners to commercialise their inventions and enforcetheir patent rights against infringers”. US Representative Bob Goodlatteinsisted that the Innovation Act would help “curb abusive patentlitigation” based on “weak or poorly-granted patents”. G

IN BRIEF

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MARKET NEWS


A“rapid reaction” is needed to address declining turnover and“stagnant” volumes in France’s generics market, according to

local industry association Gemme. Generics sales fell by 4% toC3.30 billion (US$3.74 million) in 2014, Gemme said, citing datafrom local market researcher GERS, while volumes improved byjust 2% to 800 million units.

GERS’ figures indicated that generics enjoyed an 18% valueshare of France’s reimbursable pharmaceutical market, and a shareof almost a third by volume.

Moreover, Gemme pointed out, if a constant ‘perimeter’ ofproducts was applied – excluding from the comparison new launchesin 2014 – value sales would have fallen by 8% to C3.16 billion lastyear, while volumes would have declined by 2% to 769 millionunits. “Market progress is only being supported by new launches,”the association observed.

Insisting that the “worrying” decline demonstrated the “absolutenecessity” to overhaul France’s prescribing structure, Gemme alsonoted that the fall in value was due to “massive price cuts appliedin 2014”, which had wiped around C220 million off generics turnover.This “blind” policy of price cuts was putting at risk continuity ofsupply, the association warned.

Gemme’s president, Pascal Brière, noted that using genericmedicines had saved France around C2 billion in 2014. But “if genericmedicines were used in the same proportions as in Germany and theUK”, he noted, “these savings could be doubled”.

Meanwhile, a report by market researcher GlobalData hasforecasted that France’s overall pharmaceutical market will achievea compound annual growth rate (CAGR) of just 0.7% from 2014 to2020, “restricted by an increasing focus on generic drugs”.

While France had been a “relatively late entrant to the genericsmarket”, GlobalData said, the researcher expected generics volumesto “shift closer to levels seen in the rest of Europe”, restricting overallgrowth for pharmaceuticals. G

Reducing data exclusivity for branded biologics from 12 years toseven and prohibiting additional exclusivity periods for such drugs

for “minor changes in product formulations” would save the US aroundUS$16 billion over 10 years, according to proposals set out in thecountry’s 2016 budget. Other measures aimed at lowering costs forthe Medicaid insurance programme – including collecting additionalrebates for generics with prices that grow faster than inflation, andexcluding authorised generics from average manufacturer pricecalculations – would save a further US$6.3 billion, the document states.

Local brand biologics association the Biotechnology IndustryOrganization (BIO) said reducing data exclusivity would “jeopardisethe careful, overwhelmingly bipartisan balance established in the lawto reduce costs, expand access, and encourage continued innovation”.

Meanwhile, the US Food and Drug Administration (FDA) saidit had requested an overall budget of US$4.9 billion, which FDACommissioner Margaret Hamburg said “accurately reflects thechallenges FDA faces in a global regulatory environment, which isbecoming increasingly complex and scientifically demanding”. G

France must addressdeclining sales trend

MARKET RESEARCH

US looks for biologics savingsREGULATORY AFFAIRS

CGPA – the Canadian Generic Pharmaceutical Association – haswelcomed savings that will be generated through a healthcare‘action plan’ set out by the government of Ontario, Canada. However,the association insisted that higher usage of generics was essentialto unlock greater savings in the Canadian province. “If Ontario’sutilisation of generic drugs increased to the same levels as in theUS,” the association said, stating that generics were dispensedto fill 86% of US prescriptions, “it would save the province’shealthcare system more than C$2.6 billion (US$2.1 billion) inthe first year alone.”

ROMANIA’s mandatory pharmaceutical clawback rising to morethan 25% in the last quarter of 2014 is “unsustainable” and willbe “catastrophic for both patients and generic manufacturers”,according to local generics industry association APMGR. Notingthat the 25.23% clawback was “the highest level calculated to date”,APMGR’s president, Dragos Damian, said the rise – from 20.92%in the third quarter of 2014 – did “not correlate in any way to internalcompany data on growth in drug consumption”. The clawback hadalready forced generics firms to cut 300 jobs and reduce productionby a tenth in 2014, APMGR noted, appealing to Romania’sgovernment to intervene in the clawback calculation.

SPAIN must introduce a national policy framework to encouragethe uptake of biosimilars, local generics industry association Aeseghas told a conference including representatives from the country’scongress and senate. Aeseg’s director-general Ángel Luis Rodríguezde la Cuerda said specific rules recognising the special characteristicsof biosimilars were needed, rather than relying on the existingreference-pricing system for small-molecule generics.

SOUTH AFRICA will allow a maximum increase of 7.50% in thecountry’s Single Exit Price (SEP), the uniform price for eachproduct that manufacturers must offer to all private customers.Companies have until 13 March to submit revised prices. Theincrease – which follows a 5.82% rise last year (Generics bulletin,14 February 2014, page 9) – does not apply to products introducedafter 23 December 2014.

AUSTRALIA must address “significant market barriers” to theregulation and reimbursement of biosimilars, according to thecountry’s Generic Medicines Industry Association (GMiA). Marketentry barriers – also including obstacles to prescribing and dispensingbiosimilars – need “urgent attention”, the GMiA said, recommending“the implementation of a clear and predictable market accesspathway, with uptake drivers, for biosimilars”.

RUSSIA’s Civic Chamber has urged the country’s Ministry ofHealth to launch an information campaign to advise the public ofdomestically-produced generic alternatives to branded medicines.The Civic Chamber claimed that large pharmaceutical firms basedoutside Russia were providing financial incentives for doctors andpharmacists to prescribe and dispense originator products at thesame time as “unreasonable” price increases were being appliedto certain brands.

QATAR’s Supreme Council of Health (SCH) has cut the prices of457 generics by an average of 28.5% as part of a scheme to unifyimport prices for Gulf Cooperation Council countries. Noting thatthe drugs included cardiovascular, endocrine, musculoskeletal,dermatological and gastrointestinal treatments, the SCH said somemedicines had prices cut by as much as four-fifths. A further waveof price cuts will be implemented in the second half of this year. G

IN BRIEF


MARKET NEWS


Reducing unnecessary litigation and accelerating approvals ofabbreviated new drug applications (ANDAs) and hybrid 505(b)(2)

applications are among the stated goals of a proposed rule the US Foodand Drug Administration (FDA) has released for public commentuntil 7 May. Having for the past decade implemented the 2003Medicare Modernization Act (MMA) directly from the statute, theFDA now plans to amend its regulations to codify parts of the actcovering 30-month stays on approval and other matters not related to180-day generic market exclusivity.

Among the proposed measures are: tackling originators includingoverly broad use codes for patents listed in the FDA’s Orange Book;treating original and reissued patents as a ‘single bundle’ of patentrights; and clarifying the agency’s practices on patent information thatis submitted late. The FDA is also proposing to accept paragraph IVcertifications to newly-listed patents only from the first working dayafter the patent is published in the Orange Book.

Also included in the proposals are plans to revise the content thatmust be included in notices of paragraph IV certifications. The FDAalso plans to “clarify and augment the patent certification requirementsfor amendments and supplements to 505(b)(2) applications and ANDAsto ensure that changes to the drug product that could be protected bypatent are accompanied by a new patent certification”.

Another rule involves requiring 505(b)(2) applicants to identifya pharmaceutically equivalent product if one is already approved. Thisis “to help ensure that the 505(b)(2) pathway is not used to circumventthe statutory patent certification obligations that would have appliedif the product was not ineligible for approval in an ANDA”.

The FDA also intends to “codify current practice” by clarifyingthat 30-month stays of approval for ANDAs or 505(b)(2) applicationsbegin on “the later of the date of receipt of notice of paragraph IVcertification by any owner of the listed patent or by the new drugapplication (NDA) holder who is an exclusive licensee”.

The FDA said the rule’s annual costs of US$91,400 would beoutweighed by benefits of around US$194,300. The agency has also“identified, but is unable to quantify, impacts from proposed changes tosubmitted patent information and the implementation of an administrativeconsequence for ANDA applicants who fail to provide notice of aparagraph IV certification within the timeframe required”. G

FDA unveils plans tocodify rules on stays

REGULATORY AFFAIRS

Proposals to set up a single medicines agency for drug control andregistration in Ukraine have been released for public consultation

by the country’s Ministry of Health as part of efforts to “harmonisethe country’s medicines regulations to European standards”.

At present, procedures for drug licensing, registration, import,safety and quality control, as well as inspection are controlled byseparate state authorities including the Ministry of Health and thecountry’s Service for Medicines. This, the Ministry of Health says,results in unnecessary duplication.

Citing countries that have already such agencies in place, includingthe Czech Republic, France, the UK and the US, the Ministry of Healthbelieves that implementing a “one-stop-shop” for all types of licencesand permits will benefit the industry. G

Ukraine urges a single agencyREGULATORY AFFAIRS

Canada will require manufacturers to publicly report drugshortages “for Canadians to better plan for their health and

safety”, according to draft regulations set out by the country’sgovernment. “By providing advanced warning of upcoming shortages,Canadians will be able to better proactively work with their healthcareprofessionals to find alternative options,” said Health Canada.Companies failing to comply will face fines and penalties.

The “mandatory reporting system” would see “timely,comprehensive and reliable information on actual and anticipateddrug shortages” made available on an independent third-party website,Health Canada said. “While this new website and the regulationsare being developed, manufacturers are expected to voluntarilypost information on all shortages on the industry-run website.”

“To reflect and encourage industry accountability, a publicnotification register has been launched on Health Canada’s websitethat lists all the manufacturers that fail to voluntarily post theirshortages,” the agency said. Federal health minister Rona Ambrosesaid this would help to “name and shame” manufacturers who failto provide voluntary notice.

Jim Keon, president of the Canadian Generic PharmaceuticalAssociation (CGPA), said the association’s members were currentlyreporting shortages on the voluntary website “and will comply with anynew requirements”. The CGPA and its members had “taken an activeleadership role” to lessen the impact of drug shortages, Keon insisted.

As well as working with the Canadian government and otherstakeholders through the multi-stakeholder steering committee ondrug shortages (MSSC), the CGPA noted that it had also developeda specific protocol for generics firms to notify and communicate drugshortages. “CGPA will continue to work with other stakeholders toaddress the root causes of drug shortages,” the association stated.

Voicing support for the government proposals, Canadian brandindustry association Rx&D said it was “committed to working withofficials to ensure the smooth implementation of a mandatory reportingsystem”. Noting that its members were already committed to voluntarilyreporting shortages publicly – even if “the same cannot be said forsome companies outside of our association” – Rx&D claimed that“in general, four out of five drug shortages are associated withgeneric pharmaceutical companies”. G

Canada will requireshortage notification

MARKET RESEARCH

Ensuring “rapid access to safe and effective medicines of goodquality for the treatment of priority diseases” is the goal of a

medicines registration harmonisation project that has been launchedin West Africa. Led by the New Partnership for Africa’s Development(NEPAD) – an “African Union strategic framework” – through itstechnical working group on medicines policy and regulatory reforms,the initiative also includes other African regulatory bodies as wellas the World Health Organization (WHO) and United Nations (UN).

“Most countries that have policies in place have not developedtheir implementation plans,” the NEPAD pointed out. “This createsa gap in the execution of the existing policies and in turn affects localmedicines regulation.” A common action plan for the entire WestAfrica region is envisaged. G

West Africa seeks alignmentREGULATORY AFFAIRS


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Manufacturers of generics that are registered in Russia before 1July 2015 may have to rerun trials demonstrating that their

versions can be considered as interchangeable with equivalent brands,according to draft legislation on approval procedures for determininginterchangeability between medicines that have been developed bythe country’s Ministry of Health. However, herbal and homeopathicproducts, as well as medicines that have been marketed for more than20 years, are exempt from the requirement.

The draft – which has been released for public consultation until13 April – is split into five sections covering general provisions;interchangeability criteria; procedures for determining interchangeabilityof first-time registered medicines; medicines registered before 1 July;and procedures for verifying interchangeability. If passed, it willcomplement other bioequivalence legislation that is expected to comeinto force on 1 July (Generics bulletin, 5 December 2014, page 15).

Meanwhile, Nikolai Gerasimenko, deputy chairman of the Russianparliament’s health committee, has urged the country to review importduties on pharmaceutical substances and certain medicines to helpbolster the domestic pharmaceutical industry as part of Russia’s “Pharma2020 strategy”. During a parliamentary debate, Gerasimenko proposedtemporarily to introduce a reduced or zero rate of customs duties onimported substances and vital drugs until more favourable conditionsfor local manufacturing were met.

“According to the Pharma 2020 strategy, 90% of pharmaceuticalsshould be produced locally by 2018”, Gerasimenko noted. “However,90% of Russian drugs are made using imported components”.Moreover, plans for setting up production facilities for active substancesin Russia had not been laid out yet, he emphasised.

At the same time, Russia’s deputy prime minister, Igor Shuvalov,has proposed setting up a pilot project by 2018 to help reduce medicinescosts by introducing a regulatory framework for parallel imports ofmedicines into the country.

However, local manufacturers opposed to the scheme have warnedthat the Russian pharmacopeia is “very different” to that of Europe,insisting that further regulatory harmonisation is needed. Moreover,they have raised concerns over labels, packaging and instructionsappearing in a foreign language. G

MARKET NEWS


REGULATORY AFFAIRS

Russia could requirenew round of tests

Interested parties have until 6 April to comment on whether theinformation the US Food and Drug Administration (FDA) intends

to collect in biosimilar applications and supplements to supportinterchangeability are necessary and “will have practical utility”.

The agency also wants to hear about ways to “enhance the quality,utility and clarity” of some information while minimising the burdenon respondents. Based on its experience to date, the FDA expectsto receive five biosimilar applications per year, each requiring theapplicant to spend 860 hours compiling the necessary information.But each notification of a patent dispute will take just two hours.

Meanwhile, five FDA draft guidances covering the 2012 GenericDrug User Fee Amendments (GDUFA) are now open for commentuntil early March after the agency reopened the docket in responseto requests for additional time.

Having first been issued by the FDA last year before a full-daypublic hearing on 17 September (Generics bulletin, 5 September 2014,page 16), the five guidance documents cover: the content and formatof abbreviated new drug applications (ANDAs); refusal to receivefor lack of proper justification of impurity limits; amendments andeasily correctable deficiencies; prior-approval supplements; andcontrolled correspondence related to generic-drug development. G

Input is invited overUS interchangeability

REGULATORY AFFAIRS

None of the medicines that have been called into question in theEuropean Union (EU) over bioequivalence studies conducted by

GVK Biosciences are currently on the Swiss market, according tolocal medicines agency Swissmedic.

After the European Medicines Agency (EMA) recommended theEuropean Commission to suspend hundreds of marketing authorisationsin the EU based on concerns raised following an inspection of GVK(Generics bulletin, 6 February 2015, page 17), Swissmedic said it hadconfirmed through “comprehensive analysis” that no correspondingpreparations were available in Switzerland.

However, Swissmedic observed, “three preparations with exportauthorisations were identified”. These authorisations – granted forproducts intended exclusively for export – would now be “reviewedin detail”, the regulator stated. G

Swiss not affected by GVKREGULATORY AFFAIRS

Eli Lilly is maintaining its pursuit of damages from the Canadiangovernment under the North American Free Trade Agreement

(NAFTA) for “illegal” decisions to invalidate brand patents, despite acounter-filing from the government backing the decisions. “Nothingin their filing changes our strongly-held belief that Canada’s improperinvalidation of our patents under its unique and burdensome ‘promise’utility is inconsistent with Canada’s NAFTA obligations,” the firmsaid. Action was initiated in 2013 over decisions to invalidate patentsprotecting Lilly’s Strattera (atomoxetine) and Zyprexa (olanzapine)brands (Generics bulletin, 6 September 2013, page 23). G

Lilly keeps up Canada attackPATENT LITIGATION

Reviews of payment and reimbursement mechanisms are neededin the UK to “deliver maximum value and sustain the market”

for generics and biosimilars, according to the British GenericManufacturers Association (BGMA). “New thinking is needed ifpatients are to benefit from the more complex medicines that genericmanufacturers are increasingly producing,” said BGMA directorgeneral Warwick Smith.

“The traditional generic market in the UK has been enormouslysuccessful, saving the National Health Service (NHS) billions of poundsannually,” Smith observed. “But we are also seeing the developmentof ever more complex medicines which will revolutionise patientoutcomes.” These included biological drugs, Smith said, as well as“greater incremental innovation” in areas such as delivery systems,combinations or patient-care packages. G

BGMA urges new approachPRICING & REIMBURSEMENT


Major changes on quality – moving away from punishingmanufacturing deficiencies to incentivising industry to adapt a

culture of quality – are underway at the US Food and DrugAdministration (FDA), according to the director of the agency’sCenter for Drug Evaluation and Research (CDER), Janet Woodcock.

Woodcock told delegates to the Annual Meeting of the US GenericPharmaceutical Association (GPhA) in Miami, US, this month thatCDER planned to “radically change the way we do things on regulatingquality”. The goal of initiatives such as setting up an Office ofPharmaceutical Quality (OPQ), coordinating inspections moreeffectively and implementing a harmonised information-technologyplatform was, she said, to incentivise industry to make high-qualitydrugs “without extensive regulatory oversight”.

Bringing together around 1,000 staff in the OPQ would, Woodcockinsisted, give CDER “one quality voice” for generics and brands, andhelp the agency move away from “giving out tickets” to performingsurveillance of quality based on metrics and site inspections.

A Program Alignment Group (PAG) was ensuring that CDER wasimproving coordination between reviewers and field inspectors withinthe FDA’s Office of Regulatory Affairs (ORA), Woodcock noted. Andan information-technology platform was collating in a single repositoryinformation on registered facilities, field reports and inspection history.

“We welcome the agency’s focus on quality, including its workto enhance inspection protocol,” stated the GPhA’s president andchief executive officer, Ralph Neas. Applauding the FDA’s “stridestowards process improvements and structural evolution”, Neas expressedoptimism that the agency would start to clear a backlog of around4,000 abbreviated new drug applications (ANDAs) awaiting approval. G

GPHA ANNUAL MEETING


REGULATORY AFFAIRS

CDER pledges a raftof ‘radical changes’

GPhA – the US Generic Pharmaceutical Association – will soon askits members to vote on proposed changes to its bylaws that wouldenable the association to create a biosimilars division. Acknowledgingthat several originators, either alone or through alliances withgenerics players, were developing biosimilars, GPhA chairmanCraig Wheeler said the division would have a separate budget andboard. The division’s chair would sit on the full GPhA board, whichwould ensure that the division acted consistently within theassociation’s broader goals and vision.

GLOBAL GENERICS SALES are approaching US$200 billionannually, according to IMS Health’s Doug Long. In the 12 monthsended September 2014, turnover grew by 10% to just over US$195billion. Volume growth was 5% to almost 1.02 trillion standard units.“The US and ‘pharmerging’ markets generate most of the genericsvalue sales. The volume growth rate is declining,” Long observed.

EXPRESS SCRIPTS is the winner of the GPhA’s inauguralOutstanding Partner Recognition. Handing the award to ExpressScripts’ vice-president of government affairs, Jonah Houts, GPhApresident and chief executive officer Ralph Neas described thepharmacy benefits manager as “one of the staunchest and mosteffective allies” the association had. Noting that Express Scriptshandled more than 1 million prescriptions each day, Neas praised thecompany for sponsoring research on biosimilars’ savings potential.G

IN BRIEF

Around 1,000 target action dates (TADs) – internal deadlines forthe US Food and Drug Administration (FDA) to act on pending

abbreviated new drug applications (ANDAs) – are to be assigned bythe end of March this year. “The TADs will be March to September2015,” stated Kathleen Uhl, who was recently made the permanentdirector of the FDA’s Office of Generic Drugs (OGD).

Delivering the keynote address at the 2015 Annual Meeting ofthe US Generic Pharmaceutical Association (GPhA) in Miami, US,Uhl described assigning TADs and notifying applicants as “a workin progress”, as the agency finalised plans on how to communicateits plans to industry.

Such TADs, Uhl stressed, applied only to ANDAs, and not toprior-approval supplements (PASs). Setting such target dates was notrequired by the Generic Drug User Fee Act (GDUFA), she explained,adding that the agency would regard an action as a final or tentativeapproval, or as a complete response letter.

Target dates for pre-year-3 ANDAsUhl said OGD’s goal was to assign TADs for all ANDAs submitted

before the third year of GDUFA started on 1 October 2014, afterwhich the agency is to review and act on 60% of original ANDAsubmissions within 15 months from the submission date. However,she said, assigning TADs would occur gradually “and with caveats”to enable the OGD to “manage inventory and synchronise reviewwork”, as well as to align review and inspection activities.

While TADs would be based on “workload-management factors”,the agency would make exceptions for large, first-time generics, Uhlclarified. For these drugs, it would aim to assign TADs thatcorresponded with the patent expiry dates or the earliest possible datethat the FDA could approve each ANDA. Several months before theTADs for such major first-time generics, the agency would aim toprovide “launch planning updates”, Uhl revealed, although thisremained “a work in progress”.

Acknowledging that TAD was “a made-up term” not found inlegislation, Uhl said the agency would implement target dates withoutguidance or a manual of policies and procedures (MAPP). One fixeddate assigned to each ANDA could not be exchanged for anotherTAD, she added, not least because such dates were in part dictated bythe OGD’s workload. “We may miss a TAD if we can get an ANDAto approval in a short amount of time,” she stated.

Acknowledging that the OGD had a backlog of around 3,300ANDAs pending action – plus another 700 that were with industryawaiting responses – Uhl admitted that the agency needed to “movethe freight”. At the same time, she pointed out, GDUFA had imposedfixed targets to act on applications currently being submitted.

During the first two years of GDUFA ended October 2014 – whichhad seen 2,441 ANDAs filed, more than the agency had expected –OGD had moved to White Oak, restructured into a ‘super office’ andset up an integrated information-technology platform, Uhl explained.Having exceeded Congressional targets by hiring 952 staff underGDUFA as of 19 November 2014, the agency was “in a good place”to meet its commitments, she maintained. Enhanced information-technology systems in place from 1 October 2014 were helping theOGD to coordinate reviews, correspondence, inspections and user fees.

“Your patience, feedback and input during GDUFA implementationis greatly appreciated,” Uhl told delegates. “We recognise that thishas been difficult, disruptive and painful.” G

REGULATORY AFFAIRS

OGD sets targets forANDA action dates


Apotex says it has become the first company to have two biosimilarfilgrastim applications under active review by the US Food and

Drug Administration (FDA) after the Canadian firm’s Grastofil(filgrastim) biosimilar version of Amgen’s Neupogen brand wasaccepted for filing by the agency. This follows quickly on from theFDA accepting Apotex’ filing for biosimilar pegfilgrastim – equivalentto the US originator’s US$3 billion Neulasta blockbuster – late lastyear (Generics bulletin, 16 January 2015, page 15).

Grastofil was developed through a 2008 North American andEuropean partnership with India’s Intas Pharmaceuticals that was a yearlater extended to cover pegfilgrastim (Generics bulletin, 13 February2009, page 17). Intas provides the active substance from its plant inMoraiya, India.

Around 18 months ago, Apotex secured a pan-European centralisedmarketing authorisation for Grastofil, and subsequently licensed thebiosimilar to Stada (Generics bulletin, 1 November 2013, page 14).

Noting that it would, like its pegfilgrastim candidate, marketGrastofil in the US through its ApoBiologix business, the Canadianfirm said US sales of Neupogen reached approximately US$1 billionlast year, according to Symphony Health Solutions.

Sandoz’ US biosimilar filgrastim candidate – filed with the FDAlast year (Generics bulletin, 8 August 2014, page 1) – has receivedbacking from the agency’s Oncologic Drugs Advisory Committee. G

PRODUCT NEWS


BIOLOGICAL DRUGS

Apotex has filgrastimaccepted in the US

Lupin has struck an agreement with Polish firm Celon Pharma tojointly develop a generic version of GlaxoSmithKline’s US$7 billion

Advair Diskus (fluticasone/salmeterol) dry-powder inhaler in the US,Canada, Mexico and “other key markets”.

Under the agreement, Celon will supply the respiratory-diseasetreatment to Lupin, which will, in turn, hold marketing rights. Nofinancial terms were disclosed.

Vinita Gupta, Lupin’s chief executive officer, maintained thatCelon’s “experience in the development and manufacturing offluticasone/salmeterol dry-powder inhalers in Europe”, coupled withthe Indian firm’s “expertise in inhalation-product development andcommercialisation in the US and other markets”, would acceleratethe process of bringing generic Advair Diskus to global markets.

Around a year ago, the Indian firm hired Maurice Chagnaud,formerly head of Teva’s businesses in central and eastern Europe, tofurther its respiratory franchise in the role of president of Europeanoperations and head of inhalation strategy (Generics bulletin, 7 March2014, page 31). Lupin then appointed Theresa Stevens, who gainedexperience in the respiratory arena during a nine-year stint withNovartis, as chief corporate development officer (Generics bulletin,2 May 2014, page 27).

Last year, Mylan said it expected to imminently commencePhase III clinical trials for the first US generic rival to Advair(Generics bulletin, 3 October 2014, page 19), having acquired theglobal rights to develop and market a generic version of the productfrom Pfizer three years earlier.

The US generics player plans to file an abbreviated new drugapplication (ANDA) for Advair in the third quarter of this year andintroduce the first AB-rated, substitutable generic in 2016.

Meanwhile, Lupin has allied with US-based respiratory specialistInspiRX to launch in the US the “all new” InspiraChamber anti-staticvalved holding chamber (VHC) device. Under the agreement, the Indiancompany will gain the exclusive US rights to promote, distribute andmarket the product, which is said to provide a more effective deliveryfor asthma medicines, particularly for young children and the elderly. G

RESPIRATORY DRUGS

Lupin enlists Celonfor American Advair

Clarity is needed over US Food and Drug Administration (FDA)draft guidance aimed at helping applicants to obtain samples of

brands governed by a risk evaluation and mitigation strategy (REMS),according to the US Generic Pharmaceutical Association (GPhA).

Commenting on the recent draft guidance – which describes howfirms can obtain a letter from the FDA stating that bioequivalence studyprotocols contain safety protections comparable to reference listeddrug (RLD) protections (Generics bulletin, 16 January 2015, page 9) –the GPhA said it was concerned that brand companies may still“use this guidance as another tool to deny or further delayproviding RLD samples”. The agency should therefore specify thatan FDA approval letter is not a legal requirement for a brandcompany to supply samples, the GPhA suggested.

The association also recommended a 30-day clock be applied toFDA reviews of bioequivalence study protocols to help applicants“plan their development activities”. G

REGULATORY AFFAIRS

GPhA responds over REMS


Mylan has been awarded a tentative approval for its US rivals toAstraZeneca’s Nexium (esomeprazole) blockbuster, but will

have to wait until paediatric exclusivities associated with two USpatents expire later this year to receive final clearance from the USFood and Drug Administration (FDA).

According to a letter addressed to Mylan’s senior manager ofregulatory affairs, Shane Shupe, the US firm’s esomeprazole 20mgand 40mg delayed-release capsules are “safe and effective for use asrecommended in the submitted labelling”, warranting a tentative nod.But until paediatric exclusivities attached to US patents 5,690,960and 5,714,504 expire – on 25 May 2015 and 3 August 2015respectively – the FDA will not grant Mylan final approval.

Nexium is also protected by eight other US patents, but, Mylantold the FDA, no litigation was brought in response to the company’sparagraph IV patent challenges to seven of them within the 45-daywindow that would have triggered a 30-month stay on approval. Aneighth US patent covers a carved-out indication.

Teva recently became the first company to receive final approvalfor generic esomeprazole capsules after the FDA stripped Ranbaxyof its tentative approval (Generics bulletin, 14 November 2014,page 20) and, later, the Indian firm’s right to 180-day genericmarket exclusivity (Generics bulletin, 6 February 2015, page 17).

Siggi Olafsson, head of Teva’s global generics business, toldinvestors that the firm would introduce its rival to Nexium this monthinto a brand market valued at almost US$2 billion. The launch, heexplained, had been held up by AstraZeneca having changed theoriginal’s label just before Teva got its approval, requiring Teva tore-label its version. “There are quite a few applications pending atthe FDA. Of those, quite a few are on 30-month stays,” he noted.

India’s Cipla says it is supplying Teva with both the esomeprazoleactive pharmaceutical ingredient and the formulation (see page 2). G

PRODUCT NEWS


GASTROINTESTINAL DRUGS

Mylan must wait foresomeprazole in US

Actavis has terminated development of its recombinant follicle-stimulating hormone (rFSH) “as part of portfolio rationalisation”.

The firm had licensed the female-infertility treatment from Itero in2010 (Generics bulletin, 6 August 2010, page 19).

Through an alliance with Amgen, Actavis is developing fourbiosimilars. Their ABP980 and ABP215 alternatives to Herceptin(trastuzumab) and Avastin (bevacizumab) are currently in Phase IIIclinical trials, while an ABP798 rival to Rituxan (rituximab) is “clinicalready”. The firms are at the process-development stage for biosimilarErbitux (cetuximab) with their ABP494 project. Actavis is alsoindependently developing a cell line for a fifth, undisclosed biosimilar.G

BIOLOGICAL DRUGS

Actavis drops rFSH project

Teva says it is “among the first” to launch a rival to Sanofi’s Renvela(sevelamer) 800mg tablets in the UK following patent expiry. The

kidney-disease treatment is available in 180-count packs. G

KIDNEY DISEASE DRUGS

Teva launches UK sevelamer

PAR has received a tentative US Food and Drug Administration(FDA) nod for a generic rival to Takeda’s Colcrys (colchicine)0.6mg tablets. The Japanese originator recently lost its bid to havean injunction placed on Hikma to prevent the Jordanian firm fromlaunching its 505(b)(2) hybrid colchicine 0.6mg capsules (Genericsbulletin, 6 February 2015, page 20), and subsequently licensed anauthorised generic of Colcrys to Prasco.

EUROFARMA has struck a deal with Melinta Therapeutics inBrazil to market delafloxacin, “an investigational fluoroquinolone”.Under the terms of the agreement, Eurofarma will be responsiblefor obtaining regulatory approval in Brazil and will be able tomarket, sell and distribute the drug for treating acute bacterial skinand skin-structure infections. Melinta will receive a combinedupfront cash and equity payment of US$15 million, as well asmilestone and royalty payments.

ACTAVIS has sent a paragraph IV notification to Orexo andGalena Biopharma for generic rivals to the originators’ Abstral(fentanyl) 0.1mg, 0.2mg, 0.3mg, 0.4mg, 0.6mg and 0.8mg sublingualtablets. Three US patents, all of which expire on 24 September 2019and belong to new drug application (NDA) holder Galena, shieldthe analgesic. Orexo said it was “working closely with our partnerGalena to review the details of this notice letter”.

CIPLA says it has been awarded its first tender in Germany for theIndian firm’s salmeterol/fluticasone 25µg/125µg and 25µg/250µgpressurised metered-dose inhalers (pMDIs), which it markets inthe country under the Serroflo brand name. Having launched inGermany last year, Cipla also in 2014 rolled out the treatment forasthma and chronic obstructive pulmonary disease (COPD) inSweden, Slovakia, the Czech Republic and Croatia under variousfantasy names (Generics bulletin, 19 September 2014, page 21).

GEDEON RICHTER has agreed to loan US$5 million to US-basedwomen’s healthcare specialist Evestra to help advance its pipelineof innovative products into clinical stages.

BERLIN CHEMIE, a subsidiary of Italian firm Menarini, intendsto invest around C10 million (US$11 million) in constructing adistribution unit next to its existing pharmaceutical facility in theKaluga region of Russia. An 80,000 sq m unit – which is to complywith international good distribution practice (GDP) standards – willeventually form a “single logistic-production complex” with thefirm’s solid dose facility that was opened two years ago.

SANDOZ has launched US rivals to Boehringer Ingelheim’sMicardis (telmisartan) 20mg, 40mg and 80mg tablets. Six othergenerics players – Actavis, Alembic, Glenmark, Mylan, Torrent andZydus Cadila – hold approved abbreviated new drug applications(ANDAs) for the antihypertensive brand, which had sales ofaround US$174 million last year, according to IMS Health data.

FARMAK has expanded its range of nasal products by launchingphenylephrine 10ml nasal drops in Ukraine. Containing 2.5mgphenylephrine as well as 0.25mg dimetindene, the product – whichis indicated for treating allergic rhinitis, nasal congestion andotitis – is marketed under the brand name Milt.

SANOFI has sued four companies – Actavis, Apotex, Breckenridgeand Mylan’s Onco Therapies – in a New Jersey district court overparagraph IV challenges to US patents protecting the originator’sJevtana (cabazitaxel) prostate-cancer drug. G

IN BRIEF


Canada’s Federal Court of Appeal has rejected Janssen’s appealagainst a lower court’s ruling not to bar Teva from obtaining a

Notice of Compliance (NOC), or marketing authorisation, forbortezomib 3.5mg vials. “Asking a court to prohibit an NOC afterit has issued is like asking someone to close the barn door after thehorses have escaped,” the panel of three judges stated.

Noting that Teva had obtained an NOC for a generic rival toJanssen’s Velcade in December last year, the appeals judges rejectedthe originator’s argument that the Comprehensive Economic and TradeAgreement (CETA) between Canada and the European Union (EU)guaranteed it “equivalent and effective rights of appeal”. CETA, thejudges pointed out, was not yet part of Canadian law because it hadnot been implemented by statute.

Any conflict arising from Teva having recently filed an abbreviatednew drug submission (ANDS) covering a new route of administrationfor bortezomib would have to be addressed by a separate legalaction, the judges added. G

PRODUCT NEWS


ONCOLOGY DRUGS

Canada refuses a baron Teva’s bortezomib

Hospira and Pfenex have struck a deal to develop a biosimilar rivalto Genentech’s Lucentis (ranibizumab) that the two firms will

“commercialise for worldwide sales”.Under the terms of the deal, Pfenex will receive an upfront payment

of US$51 million once the collaboration receives antitrust approval.Over the following five years, the firm will be eligible to receive “acombination of development and sales-based milestone payments upto an additional US$291 million”, as well as a “tiered double-digitroyalty on net sales of the product”.

Noting that Lucentis had global sales of around US$4 billion in2014, Hospira said it would share Phase III equivalence clinical-trialcosts with Pfenex, while Hospira would be responsible formanufacturing and selling the product worldwide. An executivesteering committee comprised of equal representation from the twofirms will govern the collaboration, which includes an option for futurealliances on other products.

Pfenex’ ranibizumab candidate, ‘PF582’, is currently undergoingPhase Ib/IIa safety and tolerability trials, with secondary objectivesthat include comparative pharmacokinetic and pharmacodynamicevaluations to help demonstrate biosimilarity to Lucentis.

The ophthalmic biosimilar would “expand Hospira’s biosimilarspipeline to include a new therapeutic area”, observed the firm’s chiefscientific officer, Sumant Ramachandra. Bertrand Liang, Pfenex’ chiefexecutive officer, said the deal “further validates the product-development strength and capability of Pfenex as we continue toadvance our pipeline”. G

BIOLOGICAL DRUGS

Hospira and Pfenexdevelop ranibizumab

Mylan has been sued in a US district court by Bayer and its partnerOnyx Pharmaceuticals for submitting an abbreviated new drug

application (ANDA) containing a paragraph IV patent challenge forgeneric versions of the originators’ Nexavar (sorafenib) 200mg tablets.

Six US patents are listed against Nexavar in the US Food andDrug Administration’s (FDA’s) Orange Book, the latest of whichexpires on 24 December 2027.

Expects 180-day exclusivityAs the first company to file an ANDA containing a paragraph IV

certification, Mylan expects to be eligible for 180-day generic marketexclusivity for the kidney-cancer treatment, which had US sales ofaround US$48 million in the 12 months ended 31 December 2014,according to IMS data. Mylan is partnering with Natco on sorafenib. G

ONCOLOGY DRUGS

Mylan sued over US Nexavar

ACalifornia district court has set 2 March as the date on which itwill hear Amgen’s motion for a preliminary injunction to prevent

Sandoz from marketing a rival to its Neupogen (filgrastim) originalin the US. Amgen alleges that Sandoz has failed to follow statutoryrequirements for handling patent disputes, but the biosimilar applicantinsists it can elect not to disclose details of its application andmanufacturing practice. Last month, an advisory committeerecommended that the US Food and Drug Administration (FDA)approve Sandoz’ Zarxio (filgrastim) biosimilar with all the sameindications as Neupogen. G

BIOLOGICAL DRUGS

US court sets filgrastim date

Merck, Sharp and Dohme (MSD) has agreed a deal with theMedicines Patent Pool that will allow generics firms to “develop,

manufacture and sell low-cost paediatric versions of raltegravir incountries with the highest burden of disease, where 98% of childrenwith HIV in the developing world live”.

Greg Perry, the Patent Pool’s executive director, said the groupwas “pleased to have MSD on board as a new private-sector partnerworking with us on paediatric programmes”. The World HealthOrganization (WHO) recommends raltegravir as a component ofpaediatric third-line treatment.

“Raltegravir adds to our arsenal of paediatric licences insupporting better options for children in low- and middle-incomecountries,” Perry said, “and can benefit the most neglected sub-segment: infants and toddlers less than three years of age.” G

ANTIRETROVIRAL DRUGS

Patent Pool adds raltegravir

TWi Pharmaceuticals has announced that its US rivals to Megace ES(megestrol) 625mg/5ml and Lidoderm (lidocaine) 5% patches will

be marketed by the Taiwanese company’s US subsidiary, rather thanTeva as originally planned, following an agreement with Teva.

“TWi has assembled a sales and distribution team in the US andplans to launch several products in the US under TWi’s label this year,”the firm revealed. This meant that TWi would be able to “enjoy allthe profits derived from the products”, said TWi’s president, CalvinChen. “This is consistent with the company’s strategy.” G

WEIGHT-LOSS TREATMENTS/ANALGESICS

TWi US takes two from Teva


Adistrict-court victory won by Lupin over a US patent protectingTrizivir (abacavir/lamivudine/zidovudine) until March 2016

has been upheld without comment by a panel of three US Court ofAppeals judges.

Lupin had at the end of 2013 convinced a Delaware district courtthat its generic version of Trizivir did not infringe Viiv Healthcare’sUS patent 6,417,191. The same court found that the ‘191 patent wasnot invalid. Teva had already admitted that its ANDA for a rival toEpzicom (abacavir/lamivudine) infringed the patent (Genericsbulletin, 10 January 2014, page 19).

Delaware District Judge Richard Andrews ruled that Lupin’s useof the abacavir sulfate salt put its generic outside the scope of a keytablet formulation claim in the ‘191 patent that covered pure or ‘freebase’ abacavir. “The patentee differentiated between the pure, or freebase, form of abacavir and the salt form in the claims themselves,undermining the argument that the salt form is intrinsicallyencompassed by the free base of pure form,” Andrews stated.

Teva had stipulated to infringement under the Delaware court’sclaim construction. The Israeli firm, along with Lupin, failed in itsobviousness attack on the ‘191 patent. G

PRODUCT NEWS


ANTIRETROVIRALS

Lupin wins an appealon US Trizivir patent

Novartis has filed a suit against Russia’s BioIntegrator in a Moscowarbitration court, following the firm securing a Russian registration

for its Nescler (fingolimod) generic rival to the originator’s Gilenya0.5mg capsules in November last year.

The Switzerland-based originator demanded that the registrationfor the multiple-sclerosis drug be deemed invalid as it “has reasonablegrounds to suspect” that the Russian company had infringed six-yeardata exclusivity for Gilenya – which was registered in Russia on 17August 2010 – while establishing bioequivalence between the two drugs.

Meanwhile, BioIntegrator has responded by claiming that it had“all legal grounds” for registering Nescler, the bioequivalence of whichhad been proven though comparative pre-clinical and clinical trials.The Russian company also said that its registration was filed beforesuch legislation on data protection came into force in Russia. Moreover,it added, fingolimod “has never been patented in Russia”.

At Novartis’ request, the court has ordered the Russian Ministryof Health to present the Nescler dossier at a hearing on 11 March. G

MULTIPLE SCLEROSIS DRUGS

BioIntegrator sued on Gilenya

Oncobiologics says its ONS-3010 potential biosimilar rival toAbbVie’s Humira (adalimumab) “met the primary endpoints in

its first clinical study”. A three-arm, single-dose pharmacokineticstudy in healthy volunteers that was conducted in Leiden, theNetherlands, produced endpoints that “met the bioequivalency criteriaof geometric mean ratios within a 90% confidence interval of 80%-125%”. An exploratory ex vivo pharmacodynamic study “showedencouraging results”, the US developer said. G

BIOLOGICAL DRUGS

Oncobiologics meets endpoints

Celltrion and Hospira prepared to launch their Remsima andInflectra biosimilar rivals to Janssen’s Remicade (infliximab) in

Europe by unveiling their latest data and research at the 10th annualcongress of the European Crohn’s and Colitis Organisation (ECCO).

South Korea’s Celltrion – which launched Remsima in severalEuropean markets through local partners on 25 February (see page 26)– revealed a study suggesting that its Remsima monoclonal antibodycould reduce the cost of treating Crohn’s disease in France, Italy andthe UK by up to C336 million (US$380 million) over five years. “Thesecost savings could help improve patient access to life-changingtreatments,” the company argued.

Presenting the study as a poster in Barcelona, Spain, Celltrionsaid three pricing scenarios produced savings between 2015 and 2019across the three countries ranging from C76 million to C336 million.This calculation was based on discounts of 10%, 20% and 30% tothe originator brand, which was assumed to maintain the same pricefollowing the entry of biosimilar competition.

“Market-uptake growth was also varied in each of the scenariosat 20%, 30%, and 40%, respectively. The market share was assumed tobe 25% in the first year in all scenarios,” Celltrion noted, adding thatit had calculated the number of patients eligible for infliximabtreatment based on the prevalence of Crohn’s disease, total populationand annual population growth in France, Italy and the UK.

Furthermore, the South Korean company presented six posterson clinical experience with biosimilar infliximab during the ECCOcongress. These covered 332 patients, including children, withinflammatory bowel disease (IBD). “The safety and efficacy ofbiosimilar infliximab in rheumatoid arthritis and ankylosing spondylitishave previously been demonstrated in two pivotal clinical trials, Planetasand Planetra,” the company pointed out.

Three infusions reduce disease activityDuring a satellite symposium session, Jørgen Jahnsen, Professor of

Gastroenterology at the University of Oslo in Norway, presentedevidence of a reduction in disease activity at week 14 in 74 IBDpatients following three infusions of biosimilar infliximab.

Celltrion’s president, Stanley Hong, said the data presented atthe ECCO congress supported the decision made by the EuropeanMedicines Agency (EMA) to approve Remsima and Inflectra fortreating IBD based on extrapolating data from the Planetas andPlanetra rheumatology trials. “We are conducting prospectiveobservational and registry trials as part of pharmacovigilance in theEuropean Union (EU) and South Korea to monitor the safety ofbiosimilar infliximab,” he noted.

Hospira highlighted a poster presented during the same congressby Hungarian clinicians that detailed interim results from a nationwideobservational cohort started after biosimilar infliximab entered theHungarian market in May 2014. “For the first 90 patients – 57 withCrohn’s disease and 33 with ulcerative colitis – treated with Inflectra,”Hospira observed, “reductions compared with baseline were seen invalidated measures of disease activity after both two and six weeksof treatment.”

“Results show a comparable response in patients treated withInflectra to that expected with the reference product, Remicade,” Hospirastressed, adding that the independent Hungarian study would continueto enrol patients whom it would follow for 108 weeks for those withCrohn’s disease and for 54 weeks for those with ulcerative colitis. G

BIOLOGICAL DRUGS

Celltrion and Hospiragear up for infliximab


AUK legal battle between Actavis and Pfizer over a pregabalinmethod-of-use patent is set to continue after Justice Richard Arnold

refused Actavis’ motion for summary judgement and for Pfizer’sinfringement allegation to be struck out. Arnold also allowed Pfizerto amend its infringement stance to plead a case of subjective intention,even though the disclosure that the originator was likely to seek fromActavis could “amount to a fishing expedition”.

Arnold – who recently refused to grant Pfizer an interiminjunction preventing Actavis from offering its Lecaent (pregabalin)branded generic for indications not covered by Pfizer’s pain method-of-use patent (Generics bulletin, 6 February 2015, page 22) – wasnot convinced that Pfizer had presented “reasonable grounds” forActavis having subjective intention to infringe. But he could be wrongin “a developing area of the law”, so facts should be established at trial.

“The issue is one which is likely to be suitable for considerationnot merely by the Court of Appeal, but also by the Supreme Court,”Arnold commented.

Actavis has just launched Lecaent in eight strengths with listprices of £57.96 (US$89.82) for 56 capsules, and £86.94 for 84.

Addressing a recent finding by Hague Court of Appeal that SunPharma had infringed a second medical-use patent protecting NovartisAclasta (zoledronic acid) brand (Generics bulletin, 6 February 2015,page 22), Arnold noted that the Dutch court had held that Sun “hadthe requisite knowledge” that supplying its version via a tender waslikely to infringe indirectly Novartis’ osteoporosis method-of-usepatent. “The court took into account the fact that Sun had not takensteps which it could have taken,” he added.

Arnold agreed with Actavis that Pfizer had ignored the steps thegenerics firm had, and would, take to avoid its Bulgarian-made Lecaentcapsules from being prescribed for the patented pain indication. Inany case, he said, Pfizer had not alleged intent on the part of Actavis,merely that third-party infringement was “a foreseeable consequence”of having carved out the patented indication from the generic’s label.

“Actavis contends that these allegations ignore the fact that the non-pain market is very substantial,” Arnold remarked, adding that Pfizeraccepted that Consilient Health had avoided infringement by carvingout the patented indication from labelling for its Rewisca pregabalincapsules. Dr Reddy’s has adopted a similar approach for the Alzainbranded generic for which it has just secured UK approval. G

PRODUCT NEWS


EPILEPSY DRUGS

Pregabalin disputewill persist in the UK

Actavis has been forced to halt distribution of its generic rival toAstraZeneca’s Pulmicort Respules (budesonide) inhalation

suspension in the US. The Court of Appeals has issued a temporaryinjunction preventing further distribution of the paediatric respiratorydrug pending a hearing on the originator’s appeal against a New Jerseydistrict court’s finding that AstraZeneca’s US patent 7,524,834 wasinvalid due to obviousness.

“The temporary injunction does not address product shipped priorto its issuance,” Actavis pointed out. On 13 February, immediately uponthe New Jersey court’s obviousness ruling, Actavis had announced itslaunch of the 0.25mg and 0.5mg vials for which it had held finalapproval for two-and-a-half years, but had been unable to market dueto an injunction obtained by AstraZeneca. The New Jersey rulinglifted the previous injunction.

In April 2013, the New Jersey court had found that genericdefendants Actavis, Apotex and Sandoz did not infringe the ‘834 patent,while AstraZeneca’s US patent 6,598,603 was invalid (Generics bulletin,5 April 2013, page 12). But a few months later, the US Court of Appealsreversed and remanded the non-infringement finding on the ‘834patent, which expires on 11 May 2019, including a six-month paediatricextension (Generics bulletin, 15 November 2013, page 19).

Ruling in light of the Court of Appeals’ construction of the term‘micronised powder composition’, New Jersey District Judge RenéeMarie Bumb said prior art rendered the ‘834 patent invalid. “Evidenceclearly and convincingly demonstrates that a person of skill in theart would have had a reasonable expectation of successfully preparingthe claimed sterile budesonide compositions using four of the fiveconventional sterilisation techniques,” she decided, ordering a trial tobe held to determine damages. AstraZeneca immediately appealed.

Actavis and Sandoz currently hold US approvals for genericversions of the paediatric asthma remedy, as does Teva, which hasmarketed a generic since late 2009 under the terms of a patent-litigationsettlement reached between the Israeli firm and AstraZeneca theprevious year (Generics bulletin, 5 December 2008, page 19).

AstraZeneca reported US Pulmicort sales down by 6% to US$211million last year. Actavis said combined brand and generic sales ofbudesonide suspension totalled around US$1.1 billion in the yearended June 2014.

Meanwhile, Actavis has agreed to sell the rights to its US brandedrespiratory business to AstraZeneca for an initial US$600 million plus“low single-digit royalties above a certain revenue threshold”. Actavisinsisted the transaction would “have no impact” on its commitmentto developing generic respiratory drugs.

Actavis will sell the US and Canadian development andcommercial rights to Tudorza Pressair (aclidinium bromide) andDaliresp (roflumilast) treatments for chronic obstructive pulmonarydisease (COPD), along similar rights to its investigational ‘LAS40464’aclidinium/formoterol combination that is approved in the EuropeanUnion (EU) under the Duaklir Genuair name.

The deal includes AstraZeneca paying Actavis – which gainedthe respiratory franchise through its US$28 billion deal for ForestLaboratories last year (Generics bulletin, 7 March 2014, page 1) –an additional US$100 million, linked to Actavis agreeing to amendexisting collaborations between the two companies.

Actavis said selling the respiratory brands would allow it to focuson core therapeutic areas, pay off debt and “invest in further expansionthrough business development”. G

RESPIRATORY DRUGS

Actavis has to haltbudesonide in the US

Biocad expects to launch its Russian rival to Roche’s Avastin(bevacizumab) monoclonal antibody in the second half of 2015,

having recently submitted its registration dossier for the drug to thecountry’s Ministry of Health. The Russian company claims that itsmetastatic-cancer treatment – in which the firm has investedUS$10 million – is the first domestic bevacizumab and “does notdiffer in efficacy and safety compared to the original drug”.

Pointing out that the Russian government and patients spent atotal of RUB3.2 billion (US$48 million) on imported brandedbevacizumab last year, Biocad’s vice-president, Roman Ivanov,anticipated that with its “significantly cheaper” alternative, the firmwould “fully meet patients’ demand” for the drug. G

BIOLOGICAL DRUGS

Biocad rivals Russian Avastin


Mayne Pharma has agreed to pay up to US$15.7 million in totalto take full control of two US generics – methamphetamine

tablets and triple-dose combination butalbital/acetaminophen/caffeine(BAC) capsules – that the Australian firm currently marketsthrough local partnerships. Methamphetamine is distributed by Mylan,while Libertas Pharma markets the BAC combination.

While both products are currently marketed under a profit-sharingscheme, Mayne will through the deal acquire “full ownership” of bothgenerics, including manufacture, distribution and sales control. Theagreement for methamphetamine is due to close on 5 March, whilethe BAC deal is expected to follow by June. Mayne plans to bringmethamphetamine distribution in-house from April.

Pointing out that the market for both products was “attractive withlimited generic competition”, Mayne said the two products – for whichthe company is US market leader – were expected to add aroundUS$3.5 million annually to its earnings before interest, tax, depreciationand amortisation (EBITDA).

Meanwhile, Mayne has agreed to buy the US rights to the Doryx(doxycycline) acne treatment brand and “related assets” from Actavisfor US$50 million.

The transaction is set to close by the end of February, but Actavis –which had gained the rights to the Doryx brand through its acquisitionof Mayne’s Doryx partner, Warner Chilcott, in 2013 – will continueto distribute Doryx 75mg, 100mg and 150mg delayed-release tabletsin the US for a transition period lasting until 2 May this year.

To support the implementation of Doryx, Mayne has announcedplans to establish a dedicated US Specialty Brands division thatwill include 66 sales representatives. G

PRODUCT NEWS


ANALGESICS/ATTENTION DEFICIT HYPERACTIVITY DISORDER DRUGS

Mayne pays US$16mto control two in US

Polish firm Mabion says it has filed a registration dossier for itsrival to Roche’s MabThera (rituximab) monoclonal antibody in

Argentina. At present, the firm has submitted pre-clinical analysisand studies for its MabionCD20 version of the cancer and rheumatoid-arthritis treatment to the country’s Ministry of Health while it completesPhase III clinical trials. The company said it intended – in collaborationwith its Argentine partner LKM – to seek further marketingauthorisations for the drug in other Latin American countries, includingBolivia, Chile, Colombia, Ecuador, Paraguay, Uruguay and Venezuela.G

BIOLOGICAL DRUGS

Mabion eyes Latin rituximab

Lupin has received final US Food and Drug Administration (FDA)approval for its generic version of Allergan’s Lumigan (bimatoprost)

0.03% ophthalmic solution which the US originator discontinued in2012. The Indian firm says it intends to introduce the treatment forelevated intraocular pressure in patients with open angle glaucoma orocular hypertension in the US “shortly”. Generics players Apotex andSandoz currently hold tentative US nods for bimatoprost 0.03%ophthalmic solution. G

OPHTHALMIC DRUGS

Lupin gets US bimatoprost nod

Eight generics firms have been sued by Acorda Therapeutics forfiling paragraph IV patent challenges for generic versions of

the originator’s Ampyra (dalfampridine) 10mg extended-releasetablets. Acorda’s action has triggered 30-month stays of final USFood and Drug Administration (FDA) approval for the multiplesclerosis treatment, which had sales of US$366 million last year.

Five US patents currently protect Ampyra, the latest of whichexpires on 26 May 2027. Actavis was last year sued by Acorda forsending the originator a paragraph IV patent challenge for genericversions of Ampyra (Generics bulletin, 5 September 2014, page 23).

Meanwhile, Acorda said it would oppose an inter partes review(IPR) petition a hedge fund had recently filed with the US Patent andTrademark Office (USPTO) that challenges one of Ampyra’s five USpatents. The 30-month stay on the infringement lawsuits against theeight ANDA filers would not be impacted by the IPR, Acorda noted. G

MULTIPLE SCLEROSIS DRUGS

Eight are sued on US Ampyra

Kern Pharma says it has become the first Spanish company tomarket a biosimilar monoclonal antibody by introducing infliximab

in mid-February through a local alliance with South Korea’s CelltrionHealthcare. The Spanish firm is distributing the Remsima anti-inflammatory agent through its newly-created Kern Pharma Biologicsbiosimilars unit (Generics bulletin, 6 February 2015, page 18).

To ensure full traceability, Remsima features an adhesive labelon the vial, as well as a 2D data matrix on cartons and 100mg vialsthat details the batch number and expiration date.

“This launch marks the first in a long list of biosimilar productsand, therefore, the start of a development project which is one of themost important and strategic branches of the company in the comingyears,” stated Kern’s director, Raúl Díaz-Varela. “The goal is to expandour biosimilars portfolio through Celltrion,” he said, adding thatthis formed part of a growth and diversification strategy of offeringadded-value products.

Kern cited data from Spain’s generics industry association, Aeseg,suggesting biosimilars could generate savings of C1.50 billion (US$1.70billion) by 2020 (Generics bulletin, 21 March 2014, page 13).

Celltrion has held a centralised European authorisation forRemsima since September 2013, but paediatric extensions tosupplementary protection certificates (SPCs) protecting the referencebrand, Janssen/MSD’s Remicade, have only just expired in many ofEurope’s largest markets.

Network of alliances in EuropeThe deal with Kern in Spain forms part of a network of national

and regional alliances that the South Korean firm has struck forRemsima in Europe. In the Nordic region, Orion already markets thedrug (see pages 12 and 29), while Hungary’s Egis holds rights incentral and eastern Europe, including the Commonwealth ofIndependent States (CIS). Under the terms of a deal reached last year(Generics bulletin, 5 September 2014, page 22), Mundipharmasecured rights to market the biosimilar upon SPC expiry in Belgium,Germany, Italy, Luxembourg and the Netherlands, as well as in theUK, where an SPC extension ran until 24 February. G

BIOLOGICAL DRUGS

Spain’s Kern Pharmaintroduces infliximab


Momenta Pharmaceuticals plans to open negotiations with potentialpartners for its M834 biosimilar rival to Bristol Myers-Squibb’s

Orencia (abatacept), as well as for six undisclosed early-stage biosimilarcandidates, after Baxter chose to limit the two firms’ collaborationto an alternative to Humira (adalimumab).

On 14 February, Baxter’s right to select three biological originalsto target for biosimilar development expired without being exercised.A couple of days later, Baxter told Momenta it was terminatingcollaboration on abatacept for automimmune and inflammatory diseasessuch as rheumatoid arthritis under a deal struck three years ago(Generics bulletin, 13 January 2012, page 23).

Follows Baxter pipeline reviewNoting that Baxter had been undertaking restructuring and a

pipeline review, Momenta’s president and chief executive officer,Craig Wheeler, stated: “Our collaboration with Baxter on M923,biosimilar Humira, remains strong, and we look forward to discussionsin 2015 with potential new partners for M834, a biosimilar versionof Orencia, and our additional biosimilar programmes.”

Wheeler said Momenta – which had cash and marketablesecurities totalling US$192 million at the end of last year – wouldprefer to strike deals across a portfolio of biosimilars, rather than reachagreements for individual molecules, as it would simplify investmentsin areas such as manufacturing.

“There is a very attractive partnering environment out there,” heinsisted, adding that Pfizer’s prospective takeover of Hospira (see cover)“raises the stakes for people who want to compete in this game”.

“Orencia is a complex infusion protein which plays to our strength,and as of now there are few competitors in the hunt,” Wheeler said.“We are conducting the necessary pre-clinical and process-developmentwork to advance to the clinic in 2016.”

Baxter was aiming to enrol around 300 healthy volunteers acrossthree sites in the UK for a single-dose pharmacokinetic study for theM923 adalimumab candidate, Wheeler said. With an interim safetyanalysis for a larger patient study planned, Baxter was targetingregulatory submissions from 2017. G

PRODUCT NEWS


BIOLOGICAL DRUGS

Momenta is open tooptions on abatacept

Aspen has further bolstered its anticoagulants portfolio by agreeingto acquire the rights to Novartis’ Mono-Embolex (certoparin

sodium) injectable for US$142 million. The transaction is subject toGerman competition authorities’ approval.

As a heparin-based anticoagulant, Aspen pointed out, Mono-Embolex was in the same therapeutic category as its Arixtra(fondaparinux) and Fraxiparine (nadroparin) injectables that it boughtfrom GlaxoSmithKline for £700 million (US$1.08 billion) two yearsago (Generics bulletin, 28 June 2013, page 5). But the brand offeredthe advantage of weight-independent dosing.

The South African group noted the drug – which had sales ofC68 million (US$77.9 million) in 2013 – was currently only marketedin Austria, Germany and Switzerland. However, Aspen insisted thatthis “presented an opportunity” for the firm to launch the Mono-Embolex brand in other countries. G

ACTAVIS intends shortly to launch rivals to Reckitt Benckiser’sSubutex (buprenorphine) 2mg and 8mg sublingual tablets followingfinal US Food and Drug Administration (FDA) approval. Thetreatment for opioid dependence – which saw its first rival fromRoxane in 2009 (Generics bulletin, 30 October 2009, page 17) andhas since been joined by generic versions offered by Teva’s Barrand Akorn’s Hi-Tech Pharmacal – had branded sales of aroundUS$108 million last year, according to IMS Health data. Two yearsago, Actavis, along with Amneal, launched the sublingual tabletformulation of Reckitt’s buprenorphine/naloxone combination,Suboxone (Generics bulletin, 8 March 2013, page 16).

INTAS says its Accofil (filgrastim) biosimilar rival to Amgen’sNeupogen original has won “two prestigious tenders”, in theNetherlands and the UK. Having recently rolled out Accofil pre-filledsyringes in two strengths – 30MU/0.5ml and 48MU/0.5ml – throughits Accord Healthcare subsidiary (Generics bulletin, 6 February 2015,page 23), Intas said at the time that the biosimilar would initiallybe available in the Netherlands, followed by the UK and Poland.

ENDO and its partner BioDelivery Sciences International (BDSI)have had their new drug application (NDA) for Belbuca(buprenorphine) buccal film accepted for filing by the US Foodand Drug Administration (FDA). Having been awarded a standardreview by the agency, the treatment for severe pain will, Endoexpects, be reviewed by the agency by October this year.

STRIDES ARCOLAB has reached an agreement with Gilead Sciencesfor a licence to the originator’s investigational tenofovir alafenamide(TAF), both “as a single-agent product and in combination withother drugs”, in 112 countries. The agreement also provides for atechnology transfer from Gilead to enable the production of “low-cost versions” of the antiretroviral, pending US Food and DrugAdministration (FDA) approval of the product.

MYLAN has received US Food and Drug Administration (FDA)approval for its memantine 5mg and 10mg tablets. The nod makesit the first generic to be listed by the FDA as a rival to the Namendabrand marketed by Actavis’ Forest Laboratories.

RUSSIAN manufacturers will produce 12 pharmaceutical substancesincluding caspofungin, deferasirox and lenalidomide by 2016 as partof the country’s Pharma 2020 strategy aimed at developing domesticalternatives to imported brands. In total, the Russian government isproviding RUB4.45 billion (US$67.3 million) to support the domesticpharma companies in producing a total of 22 pharmaceuticalsubstances, including 10 that had previously been announced.

OHIO attorney general Mike DeWine has written to Amphastar’schief executive officer, Jack Zhang, requesting rebates for certainconsumers – including police departments – following “dramatic”price increases for the US firm’s generic naloxone that is used totreat narcotics overdose. Pointing to an agreement reached with NewYork attorney general Eric Schneiderman that allows for a US$6.00rebate for naloxone distributors, DeWine said a “similar agreement”would make a “tremendous difference” in Ohio.

CIPLA has won a US$189 million share of a Global Fundantiretroviral tender. The contract – which runs from the start ofthis year until the end of 2017 – covers supplies that will begin inthe near future. The Indian firm said the deal “offers us a greatopportunity to make HIV and AIDS treatment accessible to morethan 140 countries”. G

IN BRIEF

ANTICOAGULANTS

Aspen adds an anticoagulant


PIPELINE WATCH


February brought the expiry of six-month paediatric extensions tosupplementary protection certificates (SPCs) for Janssen’s

blockbuster monoclonal antibody Remicade (infliximab) in some ofEurope’s largest markets, including France, Germany and the UK (seeFigure 1). Hospira seized immediately on the end of SPCs linked toEuropean patent EP0,610,201 to launch in several countries itsbiosimilar infliximab, Inflectra, that it developed with South Korea’sCelltrion (see front page).

January and February also brought initial SPC expiries for Amgen’sEnbrel (etanercept). These SPCs were linked to European patentsEP0,464,533 and EP0,471,701. “The Portuguese equivalent of ‘533has been extended by a six-month paediatric extension until August2015,” notes Ark Patent Intelligence, which monitors patent, SPC

and data exclusivity durations. In several countries, SPCs linked toother patents have been granted six-month paediatric extensions, butall SPCs have expired in Norway and Switzerland.

The European Medicines Agency (EMA) recently accepted forreview an application for biosimilar etanercept submitted by SamsungBioepis (Generics bulletin, 6 February 2015, page 18).

In terms of data exclusivity (see Figure 2), January brought theend of 10 years of data and market exclusivity for Roche’s Avastin(bevacizumab). An eight-year data exclusivity period for Novartis’Lucentis (ranibizumab) has also just ended, to be followed by a two-year market exclusivity period. Ark notes that both molecules sharea common patent family that forms the basis of SPCs running untilDecember 2019 for bevacizumab and January 2022 for ranibizumab.G

This monthly update of key patent, SPC and data exclusivity data is extracted from Ark Patent Intelligence Expiry Database. Covering 50countries and over 1,600 INNs, Ark Expiry Database contains watertight data teamed with the ultimate in generic launch analysis.

For further information, visit www.arkpatentintelligence.com, or contact:Europe: +44 870 879 0081. North America: +1 704 665 1986.Or e-mail: [email protected].

INN Country

January

Etanercept Ireland, Sweden, Switzerland, UK

Gadobutrol Belgium, Greece, Hungary, Sweden

Levosimendan Austria, Greece, Italy, Luxembourg, Sweden

Palifermin Austria, Belgium, Denmark, France, Germany,Italy, Luxembourg, Netherlands, Spain,Sweden, Switzerland, UK

Sevelamer Austria, Belgium, Denmark, France, Germany,Greece, Ireland, Italy, Luxembourg,Netherlands, Portugal, Spain, Sweden, UK

Trastuzumab Greece

February

Corifollitropin alfa Austria, Belgium, Denmark, France, Germany,Italy, Luxembourg, Netherlands, Spain,Sweden, UK

Desogestrel Portugal

Drospirenone/EE Sweden

Efavirenz Czech Republic

Emtricitabine Slovenia

Etanercept Austria, Belgium, Denmark, France, Germany,Greece, Italy, Luxembourg, Netherlands,Norway, Spain

Fluticasone/Salmeterol Cyprus

Infliximab Austria*, Belgium*, Denmark*, France*,Germany*, Italy*, Luxembourg*, Netherlands*,Spain*, Sweden*, UK*

Nesiritide Switzerland

Paliperidone Portugal

Rizatriptan Czech Republic

* indicates expiry of paediatric extension to the SPC

Figure 1: Molecules for which supplementary protection certificates (SPCs) expire inkey markets during January and February 2015 (Source – Ark Patent Intelligence)

SPC expiries in January/FebruaryINN Country/Region

JanuaryAmlodipine/Valsartan European Union**Bevacizumab European UnionBortezomib SwitzerlandCertolizumab pegol AustraliaDeslorelin Belgium, France, Germany, Italy, Luxembourg,

Netherlands, Sweden, UKEculizumab Canada*Fampridine USLiraglutide USMetformin/Linagliptin USPemetrexed SwitzerlandRanibizumab European Union**Trilostane Canada*

FebruaryClodronic acid SwitzerlandDarunavir European Union**Degarelix AustraliaDesvenlafaxine Canada*Emtricitabine/Tenofovir European UnionEplerenone Canada*Lisdexamfetamine Canada*Nitisinone European UnionRasagiline European UnionRomiplostim Canada*Treprostinil European UnionVelaglucerase alfa USZiconotide European Union* This will be followed by a no-marketing period of two years during which a notice ofcompliance will not be granted to a generic manufacturer. In addition, a further six monthsdata protection will be added to the 8-year term for studies of desvenlafaxine, eculizumab,eplerenone, lisdexamfetamine, romiplostim and trilostane in paediatric populations.

** This will be followed by a no-marketing period of two years during which a genericmay not enter the market in the European Union.

Data exclusivity expiries in January/February

Figure 2: Molecules for which data exclusivity expires in key markets duringJanuary and February 2015 (Source – Ark Patent Intelligence)

Remicade expiries open options in Europe


Norway will be able to procure a biosimilar version of infliximabat a 72% discount to the existing brand price, according to the

results of a tender announced by local procurement organisation LIS.Orion offered Remsima at a 72% discount to the current price forRemicade, and a 69% discount to the lowest price offer made byMerck, Sharp and Dohme for the brand version as part of the tender.

LIS said Orion had offered Remsima for treating rheumatoidarthritis at a cost of NOK26,011 (US$3,418) per patient for a courseof treatment, compared to an offer of NOK41,244 for Hospira’s Inflectraand NOK83,438 for Remicade.

Saves NOK57,000 per patientChoosing Remsima over Remicade would therefore save

NOK57,427 per patient, LIS pointed out (see Figure 1).For treating ankylosing spondylitis, Crohn’s syndrome, psoriasis,

psoriatic arthritis and ulcerative colitis, the procurement cost ofRemsima was NOK43,352, compared to NOK68,740 for Inflectra andNOK139,063 for Remicade. This would save NOK95,711 per patient.G

PRODUCT NEWS


BIOLOGICAL DRUGS

Norway enjoys steepinfliximab price cut

1401301201101009080706050403020100

NO

K(t

hous

ands

)

Rheumatoid arthritis Ulcerative colitis

Remsima

Remicade

26,011

83,438

43,352

139,063

57,427savings

95,711savings

Figure 1: Price offers submitted to LIS for a course of treatment of Orion’sRemsima and MSD’s Remicade infliximabs for treating rheumatoid arthritis andulcerative colitis (Source – LIS)

Medical charity Doctors of the World has filed an opposition againsta European patent protecting Gilead’s Sovaldi (sofosbuvir)

hepatitis C treatment. The opposition against the EP2,203,462 patentsubmitted to the European Patent Office (EPO) puts forward severalgrounds of objection, including lack of novelty and inventive step.

“This is the first time any medical organisation has challengeda drug patent in Europe,” the charity claimed. Citing “the exorbitantprice” of £33,000 (US$50,735) per course of treatment with Sovaldiin the UK – and a similar price in France – the charity said “genericversions of sofosbuvir can be produced for as little as £66”. Within theEuropean Union (EU), it added, 7.3-8.8 million people were estimatedto be infected with hepatitis C, but “several hundred thousandindividuals” were being denied access due to the price.

The ‘462 patent, Doctors of the World alleged, was “clearly aimedat reserving an unexplored field of research, instead of protectingfactual results of successful research”.

On 20 February, Mylan, Polpharma and Teva each filed oppositionsto the ‘462 patent with the EPO. G

HEPATITIS C DRUGS

Doctors challengeEU sofosbuvir patent

Glaucoma patients are more likely to adhere to their medicationwhen switched from a brand to a generic drug, according to a

study of 8,427 patients published online by Ophthalmology, thejournal of the American Academy of Ophthalmology.

Researchers from the University of Michigan examined data takenfrom patients taking a prostaglandin analogue (PGA) – such aslatanoprost, bimatoprost or travoprost – 18 months before and afterthe first US generic PGA was introduced, Pfizer’s Xalatan(latanoprost), four years ago (Generics bulletin, 8 April 2011, page 22).

Adherence in patients who switched from Lumigan (bimatoprost)to generic latanoprost improved on average from 47% of the time to61% of the time, while for Travatan (travoprost) that figure increasedfrom 43% to 54%. Researchers speculated that the lower cost of thegeneric was the “primary reason” for improved compliance.

“Individuals’ out-of-pocket costs for glaucoma medications canexceed US$100 per month,” the study noted. G

OPHTHALMIC DRUGS

Xalatan rivals aid compliance

Eagle Pharmaceuticals has licensed its EP-3102 rapid-infusionalternative to Treanda (bendamustine) to the injectable oncology

brand’s owner, Teva, in a deal worth up to US$120 million. Treandahad sales of US$767 million last year, Teva reported (see page 4).

Under the exclusive US licence, Teva will waive its orphan-drugexclusivities for chronic lymphocytic leukaemia (CLL) and non-Hodgkinlymphoma (NHL) to accelerate EP-3102’s market entry. Eagle – whichhas just submitted a new drug application (NDA) and requested priorityreview by the US Food and Drug Administration (FDA) – believesits ready-to-dilute, rapid-infusion 50ml formulation may qualify forseven-year orphan exclusivities for both CLL and NHL.

Teva will pay Eagle an initial US$30 million, and up to US$90million in additional milestone payments. Moreover, the US firm willreceive unspecified double-digit royalties on future sales by Teva.

The Israeli firm will be responsible for promoting and distributingEP-3102 – which was recently found by a clinical trial to bebioequivalent to the original, but able to be administered more quickly(Generics bulletin, 16 January 2015, page 8) – while the US companywill be in charge of regulatory approvals, conducting post-approvalclinical studies and initial supply to Teva.

Eagle already holds tentative FDA approval for a 505(b)(2) hybridNDA for a 100mg/4ml liquid formulation of Treanda (Generics bulletin,1 November 2013, page 17). But Teva’s orphan-drug exclusivity blocksapproval for that formulation until September this year. Eagle is alsoone of several defendants in a case over Teva’s US Treanda patent8,791,270 that will be heard by a Delaware district court. Litigationover US patent 8,445,524 was dismissed.

Meanwhile, Teva has begun shipping US generic rivals to Sanofi’sLovenox (enoxaparin) and Pfizer’s Zyvox (linezolid) injectables.The Israeli firm – which has partnered with Chemi to develop andmanufacture enoxaparin – had been waiting to launch its Lovenoxrivals since receiving final US Food and Drug Administration (FDA)approval for the anticoagulant in seven strengths last year (Genericsbulletin, 11 July 2014, page 24). G

ONCOLOGY DRUGS

Eagle strikes deal with Teva


EVENTS


4-5 March

■ World Generic MedicinesCongress Europe 2015Madrid, SpainTopics covered at this two-day conferencewill include growth strategies, pricing,biosimilars, legal issues and market trends.

Contact: Health Network Communications.Tel: +44 207 092 1210.E-mail: [email protected]: www.healthnetworkcommunications.com.

9-10 March

■ EuroPLX 57Cascais, PortugalThis meeting provides a forum for business-development decision makers to discuss andnegotiate agreements, in-licensing, marketingand distribution of patented medicines,generics, biosimilars, OTC products,medical devices and food supplements.

Contact: Raucon.Tel: +49 6221 426296 0.E-mail: [email protected]: www.europlx.com.

18-20 March

■ 2nd World-ChinaBiosimilars ForumWuhan, China“World-China Biosimilars Forum (WCBF)” isan international conference which is claimedto be the only event in China to provide aplatform of technical exchange and strategiccollaboration for Chinese biosimilar playersand regulators and global leading biopharmas.

Contact: Ray Fu.Tel: +86 21 51869310.E-mail: [email protected] online at www.wcbiosimilarsforum.com.

24-26 March

■ World-China Generics ForumShanghai, China“World-China Generics Forum (WCGF)”calls for high-quality and high-end generics,

focusing on the improvement of genericsquality and transition from imitation toinnovation. WCGF will providecommunication and exhibition platformsfor chemical drug professionals in Chinaand abroad and promote internationalcooperation and interaction.

Contact: Violet Chang.Tel: +86 21 51869310.E-mail: [email protected] online at www.wcgenericsforum.com.

23-24 March

■ EU Biosimilar Registrationand Marketing RequirementsLondon, UKAn interactive two-day training coursethat will look at practical solutions onhow to gain regulatory approval throughfast, compliant registration applications.Contact: Informa UK.Tel: +44 20 7017 7481.E-mail: [email protected]: www.pti-global.co.uk.

26-27 March

■ 11th EGA LegalAffairs ForumBrussels, BelgiumThis is a two-day event organised bythe European Generic medicinesAssociation (EGA) which will look atissues including litigation, regulatorymatters and patent settlements.Contact: Lucia Romagnoli, GPA Conferences.Tel: +44 7562 876 873.E-mail: [email protected] online at www.egagenerics.com orwww.egaevents.org.

13-15 April

■ DIA 27th AnnualEuroMeetingParis, FranceIssues to be covered at this three-day eventinclude innovation, clinical trials legislationand medical devices. There will be speakers

from firms including Amgen and Sanofi.

Contact: DIA.Tel: +41 61 225 5151.E-mail: [email protected]: www.diaeurope.org.

20-21 April

■ 3rd Annual Biosimilars &Biobetters CongressLondon, UKThis event will address topics includingmarket access and strategies. Presentationswill provide information on emergingmarkets as well as global commercialisationstrategies. The development of biosimilarsand biobetters will be the focus of day two.

Contact: Oxford Global.Tel: +44 1865 248455.E-mail: [email protected]: www.oxfordglobal.co.uk.

23-24 April

■ 13th EGA InternationalBiosimilars ConferenceLondon, UKThis meeting is organised by the EGAand will cover topics including industrydevelopments and regulatory issues forthe biosimilars industry.Contact: Lucia Romagnoli, GPA Conferences.Tel: +44 7562 876 873.E-mail: [email protected] online at www.egagenerics.com orwww.egaevents.org.

27-28 May 2015

■ World BiosimilarCongress USASan Diego, USATopics looked at during this two-dayconference will include biosimilardevelopment and regulation, clinicalstudies, reimbursement and legal strategies.

Contact: Terrapinn.Tel: +1 212 379 6322.E-mail: [email protected]: www.terrapinn.com.

8, 9-10 June

■ 6th EuropeanGMP ConferenceHeidelberg, GermanyThis two-day conference will discusscurrent and planned changes to the goodmanufacturing practice (GMP) regulation.Contact: Concept Heidelberg.Tel: + 49 6221 84 44 34.E-mail: [email protected]: www.gmp-conference.org.

16-19 September

■ 18th IGPA Annual ConferenceToronto, CanadaThis three-day event is being organised by the Canadian GenericPharmaceutical Association. It is the annual joint meeting of the Canadian, European,Japanese, Jordanian, South African and US generics industry associations, the CGPA,EGA, JAPM, JGA, NAPM and GPhA. Pharmaceutical executives have the opportunity totake part in conference workshops, and listen to industry experts discuss current issuesregarding the international pharmaceutical sector during a full schedule of plenarysessions. There are also opportunities to network.

Contact: Julie Tam, CGPA. Tel: +1 416 223 2333.E-mail: [email protected] Website: www.igpa2015toronto.com.

MMAARRCCHH

AAPPRRIILL

MMAAYY

JJUUNNEE

Gen 27-02-15 Pgs.30 Events_Layout 1 25/02/2015 18:35 Page 2

Long-term product price trends or other price analyses are available.

Please specify the product and period of time you would like toinvestigate and email your request to [email protected].

■ For further information see www.bppi.co.uk.Alternatively, contact Charles Joynson atWaveData Limited, UK. Tel: +44 (0)1702 425125.E-mail: [email protected].

WANT MORE LIKE THIS?

In June of last year, we noted that escitalopram had started life asa commodity generic, and contrasted its dramatic price fall at

launch with that of generic citalopram more than a decade earlier(Generics bulletin, 20 June 2014, page 25). Citalopram had beenintroduced in the UK at the start of 2002 with prices offering a 10%discount to the Cipramil brand. More than two years later, the averagetrade price of citalopram was still more than 50% of the brand price.

Launch prices for citalopram’s successor – effectively on Monday,2 June 2014 – offered a 90% discount to Lundbeck’s Cipralex brand.Actavis and Teva both launched immediately upon expiry of the brand’ssupplementary protection certificate on 31 May.

Looking back over the six months that escitalopram has beenon the market, it is clear that little has changed in the generic’s price,but a lot has happened to pharmacists’ dispensing margins. Theaverage prices at generic launch offered to independent pharmacistsand dispensing doctors were £0.88 (US$1.36) for the 5mg strength,£1.18 for 10mg and £2.00 for 20mg. This compared with £8.97, £14.91and £25.20 for the equivalent Cipralex strengths, or between 90%and 92% discount to the brand price.

Average trade prices for the two lower strengths were just £0.04or £0.02 lower last month than they had been the previous June. Theprice of the 20mg strength, however, had dropped to £1.76, whichrepresented a 93% discount to the brand equivalent.

Meanwhile, the Drug Tariff of pharmacy reimbursement priceshad changed in October 2014 from category C – the Cipralex tradeprice – to category M, which is based on actual generic trade pricesin the marketplace. The result was as dramatic as the price fall on Day1 and had the same effect on pharmacists’ dispensing margins. Forfour months they had enjoyed margins of 90% or more on average,but these were suddenly reduced to 44% for the 5mg strength (seeFigure 1) and as low as 33% for 20mg (see Figure 2).

Today, pharmacists’ dispensing margins are even tighter, havingfallen on average to 30% for the highest 20mg strength, 33% forthe 10mg strength and 39% for the 5mg presentation.

In terms of trade marketing activity, escitalopram got off to aslow start. Despite the large discounts on offer, WaveData onlyrecorded 10 price offers in the first full month on the market ofescitalopram 5mg from generics manufacturers and wholesalers toindependent pharmacists and dispensing doctors (see Figure 3).Similarly, there were only 14 for the 20mg strength (see Figure 4).

In subsequent months, however, the activity has been fairlyconsistent, peaking in July – the second full month after launch –with about 70 price offers, and settling to about 60 more recently.This measure of competitive activity compares with monthly scoresof over 100 price offers for the most active ‘fast movers’, such asomeprazole, lansoprazole and simvastatin.

Although the average prices of escitalopram changed little overthe six months, some suppliers questioned whether the Day 1 pricediscount had been too steep. There were shallow price peaks in Julywhen the competition started to get heated, with average prices of £1.08for the 5mg strength, £1.66 for 10mg and £2.82 for 20mg. G

PRICE WATCH ............ UK


Figure 3: Price offers for 28-tablet packs of escitalopram 5mg made each monthby generics suppliers to independent pharmacists (Source – WaveData)

Figure 2: Average trade, Drug Tariff, Brand and Parallel Import prices for 28-tabletpacks of escitalopram 20mg since generic launch (Source – WaveData)

Figure 4: Price offers for 28-tablet packs of escitalopram 20mg made eachmonth by generics suppliers to independent pharmacists (Source – WaveData)

Escitalopram discounts settle quickly

Figure 1: Average trade, Drug Tariff, Brand and Parallel Import prices for 28-tabletpacks of escitalopram 5mg since generic launch (Source – WaveData)

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Gen 27-02-15 Pg.31 Pricewatch_Layout 1 25/02/2015 18:40 Page 3

Amid a climate in which mergers and acquisitionsinvolving generics firms are not uncommon,Pfizer’s deal to acquire Hospira still stands out

for its sheer scale. And the originator’s goal with theUS$17 billion deal is similarly broad: to become aleading global player in the two “large and growingcategories” of generic injectables and biosimilars.

Acquiring Hospira will let Pfizer “vault into aleadership position in the large and growing off-patentsterile injectables marketplace”, a global market thatthe brand company said would be worth around US$70billion in 2020. The market’s compound annual growthrate (CAGR) of 10% over the next five years wouldbe driven by growth in China and the US, as well asemerging markets, Pfizer stated.

Meanwhile, the deal would also allow Pfizer to“advance its goal to be among the world’s most pre-eminent biosimilars providers”, taking a leading rolein a market that the firm said would grow to be worthUS$20 billion in 2020, as global development, regulatoryand intellectual-property pathways became clearer.

Combining the two companies reinforced thegrowth strategy of Pfizer’s Global Established Pharma(GEP) unit “to build a broad portfolio of biosimilarsin Pfizer’s therapeutic areas of strength through theaddition of Hospira’s portfolio that includes severalmarketed biosimilars,” the originator stated.

John Young, who heads Pfizer’s GEP business, saidPfizer would use its global scale and commercialnetwork to take the overall portfolio that Hospiramarketed mainly in the US and Europe into emergingmarkets in regions such as Asia-Pacific – includingChina – and Latin America.

Hospira’s “broadest portfolio in the industry”would complement the ability to develop niche genericinjectables that Pfizer had gained through last year’sUS$360 million takeover of Innopharma (Genericsbulletin, 8 August 2014, page 3), Young said. Healso highlighted the considerable capacity and lowercosts offered by Hospira’s steriles facility in Vizag,India, that is awaiting approval from the US Foodand Drug Administration (FDA).

Pfizer anticipates the transaction deliveringUS$800 million of annual cost savings by 2018, half

of which are to be delivered in the first year afterclosing, which is expected in the second half of thisyear. More than half the savings are to come fromselling and administrative expenses, with most of theremainder derived from cost of goods.

Last year, Hospira’s Specialty InjectablesPharmaceuticals business generated sales that grew bya tenth to US$3.04 billion (see Figure 1). The Devicesbusiness advanced by almost the same proportionto US$840 million, while other pharma contributedUS$589 million. Total sales that rose by 11.5% toUS$4.46 billion generated an operating margin thatrose by 10 percentage points to 10.4%.

Price increases and higher volumes in the UShelped to push up overall sales in the Americas regionby 13.5% to US$3.61 billion, or four-fifths of Hospira’stotal (see Figure 2). This rise came despite genericcompetition to the firm’s Precedex (dexmedetomidine)brand and “continued price erosion” for docetaxel.

In Hospira’s Europe, the Middle East and Africa(EMEA) region, increased volumes for biosimilars –including Nivestim (filgrastim), Inflectra (infliximab)and Retacrit (epoetin zeta) – were partly offset bycontinued pricing pressure on antibiotics and cancerdrugs, resulting in a reported sales increase forinjectables of just 0.8% to US$336 million. However,overall turnover in the region was lifted by the Devicesand contract-manufacturing units, rising by 4.6% toUS$532 million.

Meanwhile, in the Asia-Pacific region highervolumes of Precedex and “strong sales of docetaxel”in Japan across the region helped to drive a 1.1%increase in injectables sales to US$266 million. In total,Asia-Pacific sales rose by 2.6% to US$327 million, orjust over 7% of Hospira’s overall turnover.

In 2014, Pfizer’s sales dropped by 4% to US$49.6billion as turnover from the originator’s GEP unit slidby 9% to US$25.1 billion. This was in part due toincreased global competition on Lipitor (atorvastatin)that cut worldwide brand sales by 11% to US$2.06billion, as well as generic rivals to Celebrex (celecoxib)launching in the US late in 2014, which wiped a tenthoff local sales of the brand at US$1.74 billion.

Pfizer’s chairman and chief executive officer, IanRead, stressed that Pfizer intended to retain Hospira’sDevices business – which generates almost a fifth ofthe firm’s total sales (see Figure 3) – as part of GEP.

The Hospira transaction would not, Read added,affect the timing of a decision on whether to split Pfizerinto two businesses – with one covering mature productsand the other innovative and pipeline drugs (Genericsbulletin, 14 November 2014, page 10) – once theoriginator had amassed three years of financial dataat the end of 2016.

Outlining Pfizer’s current sterile injectablescapabilities, Read noted that the firm currently had“a branded portfolio of 73 products across multipletherapeutic areas, primarily resulting from historic

BUSINESS STRATEGY


Pfizer expects its

US$17 billion deal

to acquire Hospira

will make the

combined company a

market leader in both

generic injectables

and in the burgeoning

biosimilars arena.

David Wallace reports.

Pfizer eyes two top spotswith Hospira acquisition

Annual sales Reported Constant-currency(US$ millions) change (%) change (%)

Americas 2,433 +12.5 +13.2EMEA 336 +0.8 +0.7Asia-Pacific 266 +1.1 +5.8Specialty Injectables 3,035 +10.0 +11.0

Devices 840 +9.1 +10.8

Other Pharma 589 +24.4 +24.3

Hospira 4,464 +11.5 +12.5

Figure 1: Breakdown by product type and region of Hospira’s sales in 2014 (Source – Hospira)


acquisitions”. These included anaesthetics, anti-infectives, and oncology drugs.

“The addition of Hospira will greatly expand ourcapabilities through the addition of their top-tier andbroad portfolio of organically-grown sterile injectables,including acute care and oncology injectables,” Readinsisted, highlighting Hospira’s focus on first-to-marketopportunities. He also cited an “untapped demandfor generic sterile injectables in the projected medium-term in a number of markets”.

Hospira’s current generics pipeline comprises 65compounds, mostly in the areas of oncology, anti-infectives, anaesthesia and analgesia.

In emerging markets, Read observed, Pfizer’s“strong brand equity across these geographies” wouldallow Pfizer to extend the reach of Hospira’s broadportfolio into territories “where Pfizer has an extensivefootprint and strong capabilities”.

In particular, suggested GEP presidentYoung, China– where Pfizer says it has “a much larger and growingbusiness” compared to Hospira, with a “very largecommercial footprint” – was ripe with “opportunitiesfor future growth” and synergies.

Meanwhile, Young observed that “the additionof Hospira comes at a key point in the growth anddevelopment of the biosimilars segment”, with thefirm offering Pfizer “a robust in-line portfolio ofbiosimilars and expanded capabilities to capitaliseon growth opportunities”.

Hospira has just rolled out its Inflectra in 24European countries (see front page), while it also hasexclusive rights to the Celltrion-developed infliximabin the US and Canada and certain other territories.

A recent US filing for Hospira’s Retacrit biosimilarrival to two epoetin alfa-based brands – Amgen’sEpogen and Janssen’s Procrit (Generics bulletin, 6February 2015, page 19) – has now been accepted bythe US Food and Drug Administration (FDA). Thefirm is also developing filgrastim and pegfilgrastim.

And Hospira has also agreed to develop atrastuzumab candidate through a further collaborationwith Celltrion, and ranibizumab through a deal withPfenex (see page 23).

Read described discussions Pfizer would hold withHospira’s biosimilars partner, Celltrion, and potentialoverlap in biosimilar development programmes as“not a major issue for the transaction”.

Pfizer is currently enrolling for or conductingPhase III trials for rivals to Herceptin (trastuzumab),Rituxan (rituximab) and Remicade (infliximab). It hasjust completed a Phase I trial for a version of Avastin(bevacizumab) and plans later this year to launch aPhase III trial, while a Phase I trial for Humira(adalimumab) is underway.

Turning to the subject of Hospira’s past qualityand regulatory issues, Pfizer said it was “comfortablethat the issues raised by the regulators have beenaddressed or are being properly addressed”.

At the Vizag injectables plant in India that hadbeen highlighted by Young as “an important componentfor future growth and cost reduction when it comeson line”, Hospira expects to begin commercialproduction “during the first half of 2015”. In early2014, the plant received 10 ‘Form 483’ observationsfrom the FDA after a pre-approval inspection, andthe agency is still reviewing additional information

supplied by Hospira regarding corrective actions.Although FDA approval for Vizag was still pending,

Young acknowledged, “immediate approval was not anessential component of value creation in this transaction”.

Hospira is also currently in the process ofresponding to the FDA over deficiencies at its plant inIrungattukottai, India. Following Form 483 observationsreported at the facility at the end of 2013, the FDArecently performed a follow-up inspection, resultingin further observations. The firm has also recentlyresponded to FDA observations regarding its plant inMulgrave, Australia (Generics bulletin, 17 October2014, page 5).

Having recently announced that it would be closingits facility in Clayton, North Carolina, in the secondhalf of 2015 (Generics bulletin, 6 February 2015, page5), Hospira said this would result in total charges ofaround US$45 million, including a US$21.9 millionimpairment charge in the Americas segment for 2014.

However, the firm’s Rocky Mount facility – alsoin North Carolina – was upgraded by the FDA to‘voluntary action indicated’ status a year ago, and noForm 483 observations were issued after the agency’slatest inspection in June.

Despite these ongoing regulatory and complianceissues, Pfizer said it was “comfortable with thetransaction” based on a review it had completed ofHospira’s “key sites”.

“We see the addition of Hospira as providing uswith a durable growth opportunity,” Read concluded,“driven by their broad portfolios of sterile injectablesand biosimilars, technical manufacturing capabilities,and our ability to grow the portfolio with our commercialcapabilities, global scale, scientific expertise and world-class development skills.” G

BUSINESS STRATEGY

“The addition of

Hospira comes at a key

point in the growth and

development of the

biosimilars segment”


AmericasUS$3,605m, +13.5%

APACUS$327m, +2.6%

EMEAUS$532m, +4.6%

Figure 2: Breakdown by region of Hospira’s sales that increasedby 11.5% to US$4.46 billion in 2014 (Source – Hospira)

Specialty InjectablesUS$3,035m, +10.0%

Other PharmaUS$589m, +24.4%

DevicesUS$840m, +9.1%

Figure 3: Breakdown by business of Hospira’s sales that increasedby 11.5% to US$4.46 billion in 2014 (Source – Hospira)


Sanofi has named Olivier Brandicourt – currently chairman ofBayer HealthCare’s board – as its chief executive officer.Brandicourt, who joined Bayer in 2013 having previously led

Pfizer’s Emerging Markets and Established Products business units,will take the reins at Sanofi from 2 April. Until that time, Sanofi’schairman, Serge Weinberg, will remain in temporary charge.

Sanofi has lacked a permanent head since late October, whenChris Viehbacher was ousted after six years at the helm following afall-out with the board (Generics bulletin, 3 November 2014, page 1).G

PEOPLE


APPOINTMENTS

Bayer’s Brandicourtleads Sanofi as CEO

Former Teva chairman Phillip Frost has given up all responsibilitywith the company after resigning from the Israeli firm’s board.Having announced his intention to retire as chairman midway

through last year after four years in the role (Generics bulletin, 11July 2014, page 31), Frost was replaced by Yitzhak Peterburg inDecember (Generics bulletin, 5 December 2014, page 34). Frost hadjoined Teva as vice-chairman in 2006 following the Israeli firm’sUS$7.4 billion acquisition of Ivax. G

RESIGNATIONS

Frost resigns from Teva board

The US Generic Pharmaceutical Association has re-electedMomenta’s president and chief executive officer, Craig Wheeler,

as its chairman. Joining Wheeler on the GPhA’s board are Teva’sDebra Barrett, Perrigo’s Doug Boothe, Ranbaxy’s Chuck Caprarielloand Fresenius Kabi’s John Ducker, as well as Jeff Glazer fromHeritage, Peter Goldschmidt from Sandoz and Marcy Macdonaldfrom Impax. Mylan’s Marcie McClintic Coates, Lupin’s PaulMcGarty, Amneal’s Chirag Patel and Par’s Tony Pera also sit onthe board, as do Julie Reed from Hospira, Joseph Renner fromZydus and Jeff Watson from Apotex. G

INDUSTRY ASSOCIATIONS

GPhA elects Wheeler as chair

INVENT FARMA, the Icelandic company that in 2005 acquiredSpanish generics and bulk-drugs suppliers Lesvi and InkeLaboratories, has appointed Ervin Veszprémi as its chief executiveofficer. He previously headed Spanish active pharmaceuticalingredient (API) specialist Medichem.

CUSTOPHARM – the generic injectables drug-services firm based inCarlsbad, California – has recruited former Bedford Laboratoriesgeneral manager Bill Larkins to serve as chief executive officer afterit was bankrolled by US investor Water Street Healthcare Partners.Larkins led Bedford, the generic injectables business owned byBoehringer Ingelheim’s US Ben Venue subsidiary – that was recentlybought by Jordanian firm Hikma in a deal worth up to US$300 million(Generics bulletin, 6 June 2014, page 3) – from April 2012 toDecember last year. Larkins has previously worked as a director forSandoz, Pfizer affiliate Wyeth and Teva subsidiary Barr.

APMGR – Romania’s generics industry association – has re-electedDragos Damian, chief executive officer of Ranbaxy’s TerapiaRanbaxy Romania subsidiary, as its chairman and president for afurther term. Damian has served as the association’s president sinceit was established six years ago. Meanwhile, APMGR has also electedKrka’s Amelia Tataru and Sandoz’ Cezar Zaharia to its boardof directors. Along with Damian, the pair join a board consistingof Zentiva’s Simona Cocos and Teva’s Artur Banaszak.

MCKESSON has appointed Bansi Nagji as its head of corporatestrategy and business development. Nagji replaces Brian Tyler – whohas taken up the role of president of McKesson’s North AmericanPharmaceutical Distribution and Services unit – and will in his newrole report directly to the US wholesaler’s chairman and chiefexecutive officer, John Hammergren.

BOEHRINGER INGELHEIM has named Ivan Blanarik asdirector of global biosimilar development, based at the group’sheadquarters in Ingelheim. Pavol Dobrotskiy will take currentresponsibilities from Blanarik when he becomes Boehringer’sRussian general director and head of sales and marketing ofprescription medicines from 1 March.

PERRIGO has appointed Jon Michael Pardo as human resourcesmanager for the firm’s topical drugs facility in Bronx, New York.He will be responsible for employee and labour relations as wellas “strategic and operational roles” for Perrigo’s New York andNew Jersey sites. G

IN BRIEF


Actavis has unveiled the regional presidents and correspondingcountry managers that will lead its generics division once it

completes its US$66 billion merger with Allergan (Generics bulletin,5 December 2014, page 3).

Of six regional presidents, five will report to president ofInternational Generics, Lars Ramneborn. The only exception willbe Jean-Guy Goulet, head of generics in Canada and Latin America,who will report directly to incoming president of Generics and GlobalOperations, Robert Stewart, a new role created by Actavis that seesStewart replacing David Buchen as head of Actavis’ generics arm.

Only one Allergan employee, Camilla Hartvig, will oversee anActavis generics region within the proposed combination. She willbalance her role as head of generics for Actavis’ Nordics region withthose as country manager for Denmark, and oversee a team consistingof Christian Jonsson in Finland, Thordis Olafsdottir in Iceland,Fredrik Juserius in Norway and Carl-Johan Lye in Sweden.

Actavis’ Central and Eastern Europe generics business – consistingof the Baltic States, the Czech Republic, Hungary and Slovenia, Polandand Slovakia – will be led by Josef Valenta. Respectively, thosecountry managers will be Giedre Bieliauskaité, Jana Bánhidalová,Gyorgy Varadi, Izabela Zimmermann and Milan Cernek.

The company’s South Eastern Europe unit, which will fall underthe remit of Peter Bergquist, will consist of Iliya Pashov in Bulgaria,Makis Economou in Greece, Dan Ivan in Romania and PavleMarjanovic in Actavis’ Serbia and Adria segment.

Meanwhile, Grigoriy Chudakov will lead Actavis’ genericsbusiness in Russia, Ukraine and the Commonwealth of IndependentStates (CIS) and will supervise Alena Vitorskaya in Belarus, MuratNigmatov in Kazakhstan, Volodymyr Mitin in Ukraine andMoldova and Gairat Gulyamov in the Caucasus and Central Asiasegment. Chudakov will also serve as country manager for Russia.

Finally, Sara Vincent will head Actavis’ UK and Ireland unit,along with serving as country manager in the UK. Tony Hynds willoversee Actavis’ operations in Ireland.

Follows Boyer and Swanton appointmentsThese pending appointments come soon after Actavis announced

senior leadership positions within the proposed combination withAllergan, including the appointments of Andy Boyer as head of USgenerics and Wayne Swanton as head of global generics operations(Generics bulletin, 16 January 2015, page 31).

President and chief executive officer Brent Saunders andexecutive chairman Paul Bisaro will keep their respective rolesfollowing the close of the transaction.

Meanwhile, Actavis has announced that four directors will resignfrom its board as part of the company’s plans to simultaneouslyaccommodate two Allergan directors as stipulated under the mergeragreement, and reduce the size of its board from 14 to 12 membersas decided in a recent board meeting.

Announcing that Tamar Howson, John King, Jiri Michal andAndrew Turner would be leaving its board either upon the close ofthe transaction or Actavis’ 2015 annual general meeting, the companyinsisted the resignations were “not the result of any disagreement withActavis on any matter relating to its operations, policies or practices”.

The selection of the Allergan directors was “ongoing”, notedActavis, which has not yet allocated a role for the US originator’s chiefexecutive officer, David Pyott, within the proposed combination. G

PEOPLE


RESHUFFLES

Actavis reveals itslocal generics heads

US Food and Drug Administration (FDA) commissionerMargaret Hamburg has announced that she will step down at

the end of March after nearly six years in the role. Following herresignation, the FDA’s chief scientist, Stephen Ostroff, will pick upHamburg’s responsibilities on an acting basis while the agency seeksa permanent replacement.

Having being appointed commissioner in May 2009 followingnomination by US President Barack Obama (Generics bulletin, 1June 2009, page 27), Hamburg, 59, has overseen the implementationof reforms including the introduction of the Generic Drug User FeeAmendments (GDUFA) in 2012. She has also overseen the progressof a US biosimilar pathway, which has resulted in Sandoz’ filgrastimcandidate recently receiving a recommendation for approval.

Applauding the “significant progress” the FDA had made underHamburg, the US Generic Pharmaceutical Association (GPhA) said shehad been a “tireless advocate for patient safety” and a “leader in effortsto assure that FDA decisions are guided by scientific principles”.

Meanwhile, Robert Califf, vice-chancellor of clinical andtranslational research at Duke University, will join the FDA in “lateFebruary” as Deputy Commissioner for Medicinal Products andTobacco. Califf, the FDA noted, would in his new role provide “executiveleadership” to the FDA’s Center for Drug Evaluation and Research(CDER) and Center for Biologics Evaluation and Research (CBER). G

RESIGNATIONS

FDA CommissionerHamburg steps down


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