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26 April 2019No.396

Pharma IntelligenceInformaBulletin

Genericsg e n e r i c s . p h a r m a i n t e l l i g e n c e . i n f o r m a . c o m

STRATEGY

Dr Reddy’s Acquires Portfolio Of 42 ANDAs To Spur Growth In US, p. 11

INTELLECTUAL PROPERTY

US ‘Blocking-Patent’ Doctrine Comes Under Attack, p. 4

REGULATION

German Melatonin Denial Is ‘Further Blow’ To PUMA Scheme, p. 10

European Parliament Passes SPC Manufacturing WaiverDAVID WALLACE [email protected]

E urope’s off-patent industry has wel-comed the European Parliament’s decision to approve by a significant

majority a Regulation setting out a waiver that will allow firms to manufacture gener-ics and biosimilars during the term of sup-plementary protection certificates (SPCs).

“The European Parliament today voted overwhelmingly with 572 members of parliament in favour to adopt the SPC manufacturing waiver,” celebrated Eu-ropean off-patent industry association Medicines for Europe, insisting that the waiver would “improve access to medi-cine and create manufacturing job op-portunities for Europe as of July 2022.”

The SPC manufacturing waiver is now

expected to be formally adopted by the European Council within weeks. The waiv-er is due to come into force in July 2019 and companies will be able to start manu-facturing under the waiver from July 2022.

“Medicines for Europe commends the EU institutions for successfully conclud-ing this important step in the adoption of the waiver,” the association said. “We congratulate the European Commission for proposing the waiver and the rap-porteurs and shadow rapporteurs of the legal, trade and health committees of the European Parliament as well as the Euro-pean Council for substantially improving the manufacturing waiver to deliver ac-cess to medicines for European patients.”

These improvements included add-ing a provision to allow manufacturing for stockpiling for ‘day one’ launch (Also see “Two-Year Stockpiling Provision ‘Vastly Improves’ European SPC Waiver” - Generics Bulletin, 25 Jan, 2019.), although the initial-ly mooted two-year term was eventually reduced to six months, which Medicines for Europe acknowledged would be “chal-lenging” for certain complex products as well as for manufacturers producing only for local European markets who would have to quickly ramp-up production. (Also see “Deal On European SPC Manufacturing Waiver Is An Acceptable Compromise” - Ge-nerics Bulletin, 15 Feb, 2019.)

However, the association pointed out that the compromise agreement reached by the European Council, Parliament and Commission earlier this year foresees a review in five years, specifically of the day-one launch stockpiling duration.

“Today’s vote on the SPC manufactur-ing waiver reflects the EU’s commitment to access to medicines, manufacturing jobs in Europe and putting EU industry on a level playing field globally,” com-mented Adrian van den Hoven, director general of Medicines for Europe.

“Europe has everything to gain from fully implementing the waiver to enable more competition on the pharmaceutical market and to improve its own security of medicines supply.”

MUST PREVENT ‘FRIVOLOUS LITIGATION’

“The Commission has evaluated the tre-mendous investments in new, high-skill jobs that this manufacturing for export and for day one launch can deliver for Eu-

CONTINUED ON PAGE 4

scripintelligence.com

2 | Generics Bulletin | 26 April 2019 © Informa UK Ltd 2019

I N T H I S I S S U E

from the [email protected]

This week saw yet another step forward for the planned waiver that will allow European manufacturing of generics during the term of supplementary protection certificates.

As the SPC manufacturing waiver edges towards the finish line – with an endorsement by a substantial majority within the Euro-pean Parliament virtually guaranteeing the formal adoption of the Regulation by the European Council within a matter of weeks (see front cover) – the off-patent industry is still finding the measure under attack from originators.

However, this has not prevented European generics and biosimilars firms from celebrating yet another milestone for the long-awaited mechanism that will put EU-based manufacturers on a more even footing with those based elsewhere in the world where SPC protec-tion does not apply.

We have also seen a flurry of deals this week, with Jordan’s MS Pharma buying Greece’s Genepharm (p.6); Dr Reddy’s acquiring a portfolio of 42 abbreviated new drug applications to bolster its business in the US (p.11); and Aceto firming up plans to sell Ris-ing Pharmaceuticals to Shore Suven Pharma as part of bankruptcy proceedings (p.9).

Meanwhile, Generium has claimed a global first with the launch of a biosimilar of Soliris (eculizumab) in Russia (p.16), Teva and Cell-trion have together received the first Canadian nod for a rituximab biosimilar (p.14) and multi-source generic competition on testos-terone gel has kicked off in the US after the expiry of Perrigo’s 180-day exclusivity for a rival to AndroGel (p.9).

“As the SPC

manufacturing

waiver edges

towards the finish

line, the off-patent

industry is still

finding the measure

under attack from

originators”

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COVER / European Parliament Passes SPC Manufacturing Waiver

4 US ‘Blocking-Patent’ Doctrine Comes Under Attack

6 MS Pharma Acquires Genepharm In Expansion Push

8 Alvogen Targets Esmya With First European Rival

9 Aceto Moves Ahead With Rising Divestment

9 AndroGel Competitors Enter US After Perrigo’s Exclusivity Expires

10 German Melatonin Denial Is ‘Further Blow’ To PUMA Scheme

11 Dr Reddy’s Acquires Portfolio Of 42 ANDAs To Spur Growth In US

13 Teligent Has No Explanation For Sudden Share-Price Slide

14 Teva Gets Canadian Rituximab Nod But Barriers May Remain

15 UK Shortages Scheme Stands Up To Legal Scrutiny

16 Russia’s Generium Announces First Biosimilar Of Soliris

17 Sun Is Set Fair For Fenofibrate Entry In Australia

18 Rescue Plan For Debt-Laden Panacea Sees Shares Soar

Sun US Chief Gandhi Settles Insider Trading CaseTop Sun Pharma executive Abhay Gandhi and his wife have settled a case pertaining to alleged insider trading in shares of Ranbaxy around the time of the company’s acquisition by Sun from Daiichi Sankyo in 2014. Sun, which has been firefighting a raft of governance concerns, has vouched for the executive’s integrity.https://bit.ly/2GwUBM1

People Round-Up: Bhadauria Named As Amneal CSOAmneal gets a new CSO, Acino restructures its board under a new chair, the AAM adds an assistant general counsel and the British Biosimilars Association names a vice-chair, as well as other people movements from around the generics, biosimilars and value-added medicines industries.https://bit.ly/2KYUjD9

Value-Added Respiratory Round-Up: Cipla Teams With Pulmatrix For Itraconazole

Cipla has struck a deal for dry-powder itraconazole and has also launched a fine-particle beclometasone/formoterol inhaler in India. https://bit.ly/2GAlvEa

exclusive online content

Global Generics & Biosimilars Awardshttps://pharmaintelligence. informa.com/ggba

6 10 14



R E G U L AT I O N

rope,” Medicines for Europe pointed out, insisting that the waiver’s notification re-quirements – that will mean generics and biosimilars firms must disclose confiden-tial commercial information to origina-tors ahead of launch – “should therefore not be misused to block generic and bio-similar medicines competition”.

Therefore, the association said, “Medi-cines for Europe will work with its mem-bers to facilitate the practical use of the waiver and will monitor and act against any potential misuse of the notification system for frivolous litigation.”

Alfonso Calles-Sánchez, administrator within the Commission’s directorate gen-eral Grow, recently told delegates to Medi-cines for Europe’s 15th Legal Affairs Confer-ence that the Commission was preparing to start monitoring the impact of the waiver.

“After this comes into effect, we want to see, a few years later, how the waiver will work from the perspective of export industry and competitiveness. The Par-liament also insisted on looking at the impact on access to medicine,” Calles-Sánchez noted. “We will see whether stakeholders use it, and whether it was worth it, because the Commission always evaluates legislation after a few years.”

BRAND INDUSTRY CONTINUES TO PUSH BACK

However, the SPC manufacturing waiver continues to be met with a cold recep-

tion from the European brand industry.Reacting to the European Parliament’s

vote, originator body EFPIA warned that “adoption of the SPC manufacturing waiver will ultimately impact on our ca-pacity to develop new treatments for pa-tients living with diseases like cancer, dia-betes and dementia. It sends a negative

signal to the world that Europe is devalu-ing its intellectual property framework, making Europe a less attractive location for research and development, impact-ing on jobs and investment.”

“This decision to introduce the waiver creates a significant challenge for the next

mandate,” EFPIA suggested. “There is no doubt that the introduction of the waiver has weakened Europe’s research and de-velopment offering, in the face of increas-ing competition from other global regions. If Europe wants to realise its potential to be a leader in medical research and develop-ment then the next Commission will need to look for opportunities to redress the bal-ance, supporting research, development and innovation more broadly.”

The Commission could do this, EFPIA suggested, by “improving the position of Europe in fast-tracking breakthrough therapies which meet unmet health needs, by maintaining and developing Europe’s incentives and reward mecha-nisms for research and development to drive the discovery of new treatments in areas of unmet medical need and by supporting a flexible legal framework for public-private partnerships in health to foster medical R&D activities and mod-ernized manufacturing to tackle the health challenges of the future.”

“As the waiver will hit innovation in Eu-rope, the research-based industry stands ready to work with policy makers across Europe to see how we can restore interna-tional confidence in Europe as a research destination and deliver a number of prac-tical initiatives that can once again make Europe a global leader in medical research and development,” EFPIA concluded.

Published online 17 April 2019

CONTINUED FROM PAGE 1

“Today’s vote reflects the EU’s commitment to access to medicines, manufacturing jobs in

Europe and putting EU industry on a level playing field globally”

I N T E L L E C T UA L P R O P E R T Y

US ‘Blocking-Patent’ Doctrine Comes Under AttackAIDAN FRY [email protected]

A ‘blocking-patent’ doctrine ap-plied by several US district courts, as well as the Court of Appeals

for the Federal Circuit, to find patents protecting several leading brands invalid for obviousness has come under attack.

Petitions for writs of certiorari filed by both Acorda Therapeutics and Allergan plus its Saint Regis Mohawk Tribe partner call on the US Supreme Court to reconsid-er Federal Circuit findings of obviousness against Acorda’s Ampyra (dalfampridine) multiple-sclerosis brand and Allergan’s

Restasis (ciclosporin) dry-eye treatment.In September last year, the Federal

Circuit ruled in favour of Mylan, Hikma’s Roxane and Teva in invalidating all four remaining Ampyra patents, thereby opening the door for generic launches.

And at the start of this year, the court dismissed Acorda’s petition for a rehearing or rehearing en banc. (Also see “US Appeals Court Decision On Ampyra Favors Generics Players” - Generics Bulletin, 7 Jan, 2019.)

According to Acorda’s Supreme Court petition, the Federal Circuit improperly

ignored “objective indicia of non-obvi-ousness” such as commercial success, long-felt but unmet market needs and the failure of third parties to develop similar inventions and competing prod-ucts. Instead, the originator claimed, the appeals court had focused on a prior-art genus patent licensed from Elan that “supposedly ‘blocked’ other companies from developing the claimed methods.”

“The question presented,” Acorda in-forms the Supreme Court, “is whether ob-jective indicia of non-obviousness may


H E A D L I N E N E W S

be partially or entirely discounted where the development of the invention was al-legedly ‘blocked’ by the existence of a pri-or patent, and, if so, whether an ‘implicit finding’ that an invention was ‘blocked’, without a finding of actual blocking, is sufficient to conclude that an infringer has met its burden of proof.”

Arguing that the Federal Circuit “has manufactured a rigid, legally flawed doctrine that impairs patent rights and deters innovation,” Acorda insists that “by dramatically lowering the bar for successful obviousness challenges, the blocking-patent doctrine will inevitably deter pharmaceutical companies from undertaking the costly, high-risk and time-consuming research required to produce innovative drugs, like Ampyra, that can immeasurably improve the qual-ity of patients’ lives.”

On appeal, Acorda had argued that

a Delaware district court had erred be-cause a skilled person would not have had a motivation to combine the prior art to arrive at the invention, nor a rea-sonable expectation of success in doing so, and that claim limitations relating to pharmacokinetics were not inherent in the claimed invention.

SPLIT FEDERAL CIRCUIT DECISION FOUND AMPYRA PATENTS INVALID

Moreover, the originator asserted, the district court had “improperly” applied a categorical rule that the “blocking” Elan patent “negates any findings in favour of Acorda on the objective indicia of com-mercial success, failure of others, and long felt but unmet need.” All three chal-lenges were rejected by Judges Timothy Dyk and Richard Taranto, with Pauline Newman dissenting.

The Federal Circuit had in November last year affirmed without comment

a district court’s opinion that four key Restasis patents were invalid as obvi-ous. Texas district judge William Bryson had in October 2017 used his obvious-ness ruling as a platform from which to criticize Allergan’s arrangement with the Saint Regis Mohawk Tribe, transferring six Restasis patents and then licensing them back as a vehicle for sovereign immunity against legal challenges. Sovereign im-munity should not be treated as a “mon-etizable commodity” that can be bought to evade “legal responsibility”, Bryson told them. (Also see “US Restasis decision is affirmed on appeal” - Generics Bulletin, 23 Nov, 2018.)

Allergan was in early March denied a Federal Circuit rehearing. It specifically ref-erences Acorda’s case in its Supreme Court petition, and suggests that, if its petition is not granted, it could be held in abeyance until the Acorda petition is addressed.

Accusing both district and appeals courts of having employed “hindsight-based analysis” in their findings of ob-viousness, Allergan says the courts are disregarding more than 50 years of Su-preme Court precedent since its land-mark Graham v John Deere ruling in 1966 required consideration of objective of non-obviousness like commercial suc-cess and unmet need.

ALLERGAN CITED CONSIDERABLE MARKET SUCCESS OF RESTASIS

“Before Restasis,” Allergan asserts, “there was no therapy to treat chronic dry eye, despite a substantial market need.” And due to its “ground-breaking nature,” the ophthalmic brand has “enjoyed consider-able market success,” becoming a block-buster will annual sales of over $1bn.

Citing failed development projects by Alcon, Sandoz and Sirion, Allergan maintains that “both before and after

Restasis, the evidence shows others were not blocked from attempting to develop competing treatments for dry-eye dis-ease, including competing treatments using cyclosporine, but that such devel-opment was difficult, as evidenced by several failures.”

“The Federal Circuit’s expansion of the blocking-patent doctrine in both Acorda and here has made the doctrine even more dangerous,” Allergan con-tends. “Until this case and Acorda, it has only been applied to diminish evidence of commercial success – it has not been used to adversely impact the other ob-jective factors, such as long-felt need.”

SUPREME COURT WILL NOT HEAR INTER PARTES APPEAL

On 15 April, the Supreme Court denied a petition for certiorari filed by Aller-gan and the Saint Regis Mohawk Tribe in a bid to review a Federal Circuit riling from July last year that found the tribe could not assert sovereign immunity to avoid inter partes review (IPR) of Resta-sis patents which it been assigned by Allergan. (Also see “Appeals court af-firms over tribal immunity” - Generics Bulletin, 27 Jul, 2018.)

Opposing the petition, Akorn, Mylan and Teva had argued that the case was “an exceptionally poor vehicle” for con-sidering whether tribal sovereign immu-nity applied to IPRs, even if the matter warranted the Supreme Court’s atten-tion. As Allergan had paid the Saint Regis Mohawk Tribe to take nominal title to the patents and them license them back in a “cash-for-immunity deal”, the case was “a deeply tainted one”.



“By dramatically lowering the bar for successful obviousness challenges, the blocking-patent doctrine will inevitably deter pharmaceutical companies from undertaking the costly, high-risk and time-consuming research required to produce innovative drugs”

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D E A L S

MS Pharma Acquires Genepharm In Expansion Push PENELOPE MACRAE

M S Pharma, a family-run generics firm operating across the Middle East, Turkey and Africa, said it has struck a deal to acquire 100% of the outstanding shares of

Greek drugmaker Genepharm. The company called the acquisi-tion an “important milestone in our growth plans.”

Based in Jordan’s capital Amman, MS Pharma says it is aiming to enlarge its geographic footprint and reach more customers in Europe and in the rest of the world by taking over Genepharm. The Athens-based firm has 223 customers in 70 countries while MS Pharma exports to 20 nations.

The Jordanian’s firm’s chairman, Ghiath Sukhtian – who has declared an ambition to make MS Pharma “evolve into more than a family company” – said the deal should close toward the end of April. He gave no financial details about the transaction.

Sukhtian termed the acquisition of Genepharm, which devel-ops, manufactures and out-licenses high-value generics and has what he called a “strong” product portfolio, “highly complemen-tary and synergistic to our business.”

MS Pharma, which has around 2,000 employees, manufac-tures and markets pharmaceuticals ranging from cardiovas-cular, central nervous system and respiratory treatments to OTC products and supplies them to hospitals and pharma-ceutical distributors.

The acquisition of Genepharm, which combines R&D facilities with manufacturing capacity, will enhance MS Pharma’s chronic disease portfolio by adding several important products in the cardiovascular, CNS and oncology segments.

MS PHARMA SAYS ACQUISITION MUTUALLY BENEFICIALSukhtian said MS Pharma’s takeover of Genepharm also has big positives for the Greek company by allowing it “to offer a wider range of products and technologies” to its European customers. The acquisition will give Genepharm, founded in 1967, access to MS Pharma’s manufacturing plants and products portfolio. MS Pharma has plants in Algeria, Jordan, Saudi Arabia and Turkey. Genepharm’s portfolio will be strengthened with sterile inject-able products and biotechnology candidates.

MS Pharma added that plans are already in place to signifi-cantly increase the company’s development resources in Ath-ens. At its plant, the Greek firm has three manufacturing units producing conventional solid-dosage forms and oncology ster-ile-liquid dosage and solid-dosage forms.

Genepharm’s senior management, who have built a “success-ful business,” will remain with the business and “help guide” the company through its next growth phase, MS Pharma said. For its part, Genepharm said being acquired by the Jordanian company would help accelerate its growth.

Two years ago, the International Finance Corp (IFC), the pri-vate-sector arm of the World Bank, made a $45mn equity invest-ment in MS Pharma to support the company’s expansion into new markets and promote access to affordable generic pharma-ceuticals across the Middle East, Turkey and Africa.

In 2016, MS Pharma also received a $50mn investment injection from the European Bank for Reconstruction and Development to help the company develop new pharmaceutical products, diver-sify its revenue stream and enter new countries in the region.


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S T R AT E G Y

Alvogen Targets Esmya With First European RivalDAVID WALLACE [email protected]

A lvogen says it has become the first company to register a European generic rival to Gedeon Richter’s

Esmya (ulipristal), having received regu-latory clearance in “multiple European countries” after successfully concluding 16 parallel registration procedures.

“Alvogen and its business partners have filed for marketing authorization in 16 European countries using 16 decentral-ized procedures,” the company confirmed, pointing out that the ulipristal 5mg tablets were “fully developed in-house by Lotus Pharmaceuticals, an Alvogen subsidiary.”

Faysal Kalmoua, executive vice-pres-ident of Alvogen’s global portfolio, said the firm was “pleased with the approval for generic ulipristal tablets, and we look forward, with our business partners, to leading the commercialization of this im-portant product in Europe.”

Acknowledging that Gedeon Richter had already registered its own autho-rized generic – via the ‘informed con-sent’ procedure through which the reg-istration is fully based on the original Esmya dossier – a spokesperson for Al-vogen insisted that “Alvogen is the first company with a true generic” that was not a duplicate registration.

“For a small molecule [drug], regula-tions allow filing of both a DCP, a central-ized procedure and nationally in Europe,” Alvogen’s spokesperson noted. “After a thorough assessment on each of those three regulatory paths, we opted for the DCP regulatory pathway.”

DCP ALLOWS FLEXIBILITY WITH PARTNERS

Commenting on Alvogen’s decision to pursue approval through the decentral-ized procedure (DCP), the spokesperson said “we make decisions on a product-by-product basis, and for ulipristal, the DCP was the best regulatory path. As we have a significant amount of business partners – 16 – for this product, the decentralized path was much more effective in secur-ing the right flexibility for each partner.”

While Alvogen did not indicate an an-ticipated launch date, the firm said its

ulipristal “will be launched at the earliest possible timing, taking into account all potential exclusivities, including relevant and valid patents in each jurisdiction”.

SALES FELL IN 2018Responding to Alvogen’s announcement, Gedeon Richter’s communications and government relations department point-ed out that “the original product’s pro-tection expires on 20 May 2020,” mean-ing “generic Esmya products cannot be launched in the market before this date.”

The Gedeon Richter spokesperson ac-knowledged that the informed consent authorization received in 2018 “provides a theoretic opportunity for us to manu-facture the generic version of Esmya, but for the time being we cannot comment a potential launch of the generic product”.

“The usage of the ‘informed consent’ procedure is an internationally accepted approach that is legally compliant with all relevant regulations,” Richter added. “We have chosen this approach in line

with our commercial business strategy applied for Esmya.”

SALES FELL IN 2018Earlier this year, Richter reported that Es-mya sales plummeting by 72.2% to €25.9m ($29.3m) dragged Richter to a 3.0% Phar-maceutical sales decline in 2018. (Also see “Gedeon Richter Predicts Two-Year Wait To Refile Pegfilgrastim, But Teriparatide Is In The Wings” - Generics Bulletin, 14 Feb, 2019.)

The slump in sales for Esmya pertains to the European Medicines Agency’s pharmacovigilance risk assessment com-mittee (PRAC) in 2018 implementing temporary measures that included stop-ping new patients being started on Es-mya, and halting new courses of therapy being given, due to a potential associa-tion between the drug and liver injury.

Richter began to relaunch Esmya across EU markets in August and Sep-tember last year.


“As we have a significant amount of business partners – 16 – for this product, the

decentralized path was much more effective in securing the right flexibility for each partner”


D E A L S

Aceto Moves Ahead With Rising DivestmentDAVID WALLACE [email protected]

A ceto’s sale of Rising Pharmaceuticals can go ahead, the US Bankruptcy Court has decided, approving a ‘stalk-ing horse’ deal recently concluded between Aceto

and Shore Suven Pharma.Under the terms of the deal, Aceto will sell its Rising Pharma-

ceuticals unit and related businesses to Shore Suven Pharma for “gross cash proceeds of $15m, plus the assumption of operating liabilities and customer obligations related to the acquired busi-ness, on a cash-free and debt-free basis.”

The transaction is expected to close on 19 April “subject to the satisfaction of certain other conditions”.

The $15m valuation represents less than a fifth of the value of the $80m deal that Aceto agreed to acquire Rising back in 2010.

The deal comes shortly after Aceto agreed to divest its chemi-cals business assets for US$338 million through a separate ‘stalk-ing horse’ agreement – that it expects to be completed by 30 June – after filing Chapter 11 bankruptcy petitions in the US.

NO COMPETING OFFERS RECEIVED“The [Rising] sale was conducted through a court-supervised pro-cess under Section 363 of the bankruptcy code,” Aceto noted. “Un-der that process, Shore Suven Pharma’s purchase agreement served as the ‘stalking horse agreement’ and an auction would have been conducted had the company received qualified offers from other bidders reflecting potentially higher and/or otherwise better terms.”

“No such bids were received prior to the bid deadline. Therefore, no auction was conducted and Shore Suven Pharma was selected as the successful bidder.”

Aceto CEO William Kennally said the court approval “brings closure to the sales process for Rising Pharmaceuticals’ custom-ers and employees and paves the way for a seamless transition of its portfolio, customer programs and manufacturing and drug development relationships to Shore Suven Pharma.”

Shore Suven Pharma CEO Vimal Kavuru said acquiring Rising would “transform Shore Suven Pharma into a strong US generic pharmaceutical company”, adding that “leveraging Rising’s exten-sive product portfolio and vertically integrating with Suven’s world class active pharmaceutical ingredient (API) and finished-dose man-ufacturing capabilities will enable us to better serve US customers”.

ACETO DELISTED FROM NASDAQHaving in February received a notification from the Nasdaq stock market that Aceto’s common stock would be delisted as a result of the bankruptcy proceedings, Aceto appealed the notice.

However, it was ultimately unsuccessful and at the beginning of April trading of shares was suspended. “Nasdaq will complete the delisting by filing a ‘form 25 notification of delisting’ with the US Securities and Exchange Commission after the applicable ap-peals periods have lapsed,” Aceto acknowledged, stating that it would not appeal the determination.

Aceto has now commenced trading its common stock on the OTC Pink Market under the symbol ‘ACETQ’. “The transition does not affect the company’s operations,” Aceto insisted, “and does not change reporting requirements under SEC rules.”


L A U N C H E S

AndroGel Competitors Enter US After Perrigo’s Exclusivity ExpiresDAVID WALLACE [email protected]

L upin and Teva have both announced the launch of generic rivals to AbbVie’s AndroGel (testosterone) 1.62% gel in the US, following the expiry of 180-day exclusivity for Perrigo’s

generic introduced last October.Amneal and Dr Reddy’s also have approved versions listed by

the US Food and Drug Administration (FDA) with an approval date matching that of Lupin and Teva, but have not disclosed launch plans.

Generic versions of the replacement therapy for testosterone-deficiency conditions represent a substantial market opportunity. “Testosterone gel 1.62% has annual sales of more than $911m in the US, according to IQVIA data as of February 2019,” Teva pointed out.

Perrigo had launched its generic with 180-day exclusivity in

mid-October last year, as the first company to submit an ab-breviated new drug application (ANDA) containing a success-ful Paragraph IV challenge to the brand. At the time, it said the generic was facing “aggressive competition” from an authorized generic launched through Zydus.

While Perrigo is continuing to push forward with plans to separate its Prescription unit from its core Consumer Healthcare business, the firm’s CEO, Murray Kessler, recently cited the firm’s generic version of Androgel as one of the strengths demonstrat-ed by the Prescription unit.




R E G U L AT I O N

German Melatonin Denial Is ‘Further Blow’ To PUMA SchemeAIDAN FRY [email protected]

G ermany’s health technology as-sessment (HTA) body says a mel-atonin medicine approved via

a European pediatric use marketing au-thorization (PUMA) offers “no additional benefit” over alternative treatments for sleep disturbances. Germany’s medicines manufacturers’ association, the BAH, de-scribed the decision as “a further blow for the PUMA regulation.”

InfectoPharm Arzneimittel und Consili-um GmbH had earlier this year submitted to Germany’s federal joint committee, the G-BA, a dossier for its Slenyto (melatonin) 1mg and 5mg prolonged-release tablets for which RAD Neurim Pharmaceuticals obtained a pan-European centralized PUMA authorization in September last year following a positive assessment by the European Medicines Agency.

The PUMA procedure provides auto-matic access to the centralized procedure, partial fee exemptions and eight plus two years of data and market exclusivity.

The G-BA then entrusted Germany’s In-stitute for Quality and Efficiency in Health Care, IQWiG, with conducting a scientific assessment of whether Slenyto offered an additional benefit over comparable insomnia treatments that represented the “best supportive care.”

“In its dossier,” IQWiG told the G-BA, “the pharmaceutical company did not present any suitable data for assess-ing the additional benefit of melatonin in comparison to suitable therapies for treating sleep disturbances in children and youths aged two to 18 years with autism-spectrum-disorder and/or Smith-Magenis-Syndrome when sleep hygiene measures have proven inadequate.”

“From this,” IQWiG added, “there is no indi-cation of an additional benefit for melatonin versus appropriate comparable therapies; an additional benefit is thus not proven.”

IQWIG UNIMPRESSED BY INFECTOPHARM’S EVIDENCE

Addressing the clinical evidence that In-fectoPharm had included in its dossier,

IQWiG acknowledged the NEU_CH_7911 double-blind, randomized controlled tri-al comparing melatonin versus placebo in 125 children and youths aged two to 17.5 years who had autism-spectrum-disorder and/or certain neurogenetic ail-ments such as Smith-Magenis-Syndrome.

However, the institute found that this study was “not suitable”. “The placebo comparable therapy used in the NEU_CH_7911 study without employing fur-ther measures for relieving symptoms and improving quality of life does not represent an adequate implementation of the appropriate comparable treat-ment, best supportive care,” it objected. IQWiG contended that the study par-ticipants should have been offered sup-

portive measures such as sleep hygiene training or behavioural therapy as part of “the best possible treatment optimized for individual patients”.

HTA DECISION THREATENS PEDIATRIC CARE IN GERMANY

Pointing out that InfectoPharm had con-ducted specific research to demonstrate Slenyto’s use as a pediatric medicine, the BAH’s scientific director, Elmar Kroth, com-mented: “Once again, the intensive efforts of a medicines producer to improve the provision of care for children in Germany risks being thwarted through HTA.”

“That a medicine which was specially developed for children has been ascribed no additional benefit is a further blow for the PUMA regulation,” Kroth insisted. If the G-BA followed the advice offered by IQWiG, he warned that “this therapeutic option may no longer be available for children in Germany.”

Recalling that the G-BA had around six months ago denied any additional benefit for Diurnal’s Alkindi (hydrocortisone) pedi-atric formulation, Kroth cautioned: “Such decisions render uneconomical develop-ing medicines specifically for children.”

The G-BA is inviting written comments on IQWiG’s position on Slenyto until 6 May. The committee intends to reach a conclusion on Slenyto in early July.


“There is no indication of an additional

benefit for melatonin versus appropriate

comparable therapies; an additional benefit is

thus not proven”


S T R AT E G Y

Dr Reddy’s Acquires Portfolio Of 42 ANDAs To Spur Growth In USPENELOPE MACRAE

D r Reddy’s has struck a deal to ac-quire a portfolio of 42 abbrevi-ated new drug applications (AN-

DAs) in the US as it widens its offerings for its “chosen growth markets” which include the US and China.

While Dr Reddy’s did not disclose the purchase price or any other transaction details, the company said in a regula-tory filing the products had an address-able market of around $645m in calendar 2018, according to IQVIA data.

The 42 ANDAs acquired by Dr Reddy’s are already approved by the US Food and Drug Administration but have yet to be marketed. The portfolio includes more than 30 generic injectable prod-ucts, Dr Reddy’s said.

“This transaction will help augment our injectables product portfolio in the US market and globally,” said Erez Israeli, Dr Reddy’s chief operating officer.

The technology for these new ANDAs will need to be transferred to Dr Reddy’s facilities and could be launched within the next one-to-two years, the company said.

US IS A KEY GROWTH MARKETIsraeli, who is also the company’s global generics head, said the acquisition was “in line” with the Hyderabad-based compa-ny’s strategy “to significantly enhance our portfolio in our chosen growth markets.”

Back in January in a speech to the an-nual J.P. Morgan Healthcare Conference held in San Francisco, Israeli identified six key areas – the US, China, Russia, In-dia, active pharmaceutical ingredients (APIs) and hospital drugs – as under-pinning the Indian company’s growth ambitions, with small-molecule gener-ics remaining the firm’s “bread and but-ter”. (Also see “Dr Reddy’s Growth Strat-egy Sets Sights On Six Spaces” - Generics Bulletin, 11 Jan, 2019.)

At the time, Israeli said Dr Reddy’s had a pipeline of 113 products pending approv-al in the US and that “the next space” was China where he told conference delegates the Indian firm was already the largest for-

eign generics company in the country.The ANDAs acquisition dovetails neatly

with the group’s strategy for the future. After some hard times, the company has been on a roll lately with record new US launches and a recovering US market helping drive its strong financial perfor-mance. The firm also recently appointed Marc Kikuchi as chief executive officer of North America Generics.

COMPLIANCE ISSUES RESOLVEDRegulatory clouds over the company have also been lifting with Dr Reddy’s announcing on 15 April it had received an FDA establishment inspection report (EIR) for its key formulations plant at Ba-chupally in southern India, paving the way for new approvals and exports to the US. The plant accounts for 40-45% of to-tal US sales, Morgan Stanley says.

In February, in other good news, the FDA gave the all-clear to Dr Reddy’s fac-tory in Duvvada in southern India.

Analysts say Dr Reddy’s is following in the footsteps of its peers by piling vol-ume-based products into its basket of products. India’s Kotak Institutional Equi-ties said it expects the new portfolio “to be a mix of high-volume, simple-solution products with moderate-to-high compet-itive intensity.” Kotak analysts project the new portfolio by fiscal 2022 will increase

US sales by 4-5% or by $50m-$70m.Credit Suisse added that as three-

quarters of the portfolio which has been acquired consists of injectables, the com-pany might take some of these products to China and other emerging markets.

While the US drug market appears to be steadying, ongoing pricing pressures in the US drug market has prompted In-dian drug companies to look for growth in emerging markets like China with its $160bn market and analysts say Dr Red-dy’s is ahead of the pack in growing its business in the country.

Before the latest ANDA acquisition, Is-raeli said some 70 products from the Dr Reddy’s US portfolio could be eligible for marketing in China. At the same time, analysts say to really make headway in the market, Dr Reddy’s will need to find a local partner to scale up its sales in the country, which is a fiercely competitive market.

Japanese brokerage house Nomura called the ANDA portfolio acquisition “positive” from a strategic and financial vantage point while maintaining a “buy” call on Dr Reddy’s shares with a price target at INR3,414 ($49) per share which means a potential upside of more than 20%. On April 16, Dr Reddy’s was trading nearly 1% higher at INR2,816.40.



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S T R AT E G Y

Teligent Has No Explanation For Sudden Share-Price SlideAIDAN FRY [email protected]

U S niche generics specialist Teligent Inc. is unable to explain why its share price suddenly plummet-ed below $1.00, before bouncing back to $1.03 as

of midday on 15 April.“Teligent acknowledges that there have been signifi-

cant negative movements in the value of our stock over the past many days. We are not aware of any fundamental news or change in the financial condition of the company that could justify the magnitude of these changes,” com-mented the company’s president and CEO, Jason Grenfell-Gardner, in a statement released on 12 April.

Having traded a month ago at around $1.40 per share on the Nasdaq exchange, Teligent saw its valuation drop to about $1.15 by early April. The slide then picked up again, such that the closing price on 10 April dipped be-low one dollar to $0.99, reaching a nadir of $0.96 on 11 April, before recovering slightly.

Teligent’s shares had in July and August last year briefly peaked at over $4.00 each. Having given up some of those gains during September and October, the share price fell sharply after the company disappointed the financial mar-kets with its third-quarter results revealed in mid-November. By December, shares were trading at below $2.00, less than half their value a few months earlier.

Since the start of April, the only press release that Teligent had issued was on 4 April for its US approval for fluocinonide 0.1% cream, following on from US Food and Drug Administra-tion (FDA) clearance for its fluocinonide 0.05% topical solution in March. The 0.1% cream marked the company’s fourth approval to date in 2019 as it also introduced four products.

As Teligent unveiled its 2018 annual results in mid-March, the company announced that it would be late in making its 10-K annual filing with the US Securities and Exchange Commission (SEC). However, it filed that 10-K report on 1 April.

In 2018, theNew Jersey-based injectables, topicals and oph-thalmics producer made a $15.1 million operating loss on turn-over ahead by 9% to $65.9 million last year. The firm will report its financial results for the first quarter of 2019 in early May.

REITERATES FINANCIAL GUIDANCE FOR 2019Grenfell-Gardner stressed that the company continued to believe in its stated guidance for 2019 of achieving double-digit sales growth to over $72.5 million, “a consolidated gross margin above 40%, a consistent investment in R&D of $13-15 million, and an adjusted earnings before interest, tax, depreciation and amorti-sation (EBITDA) margin greater than 10% after adding back any foreign currency gains or losses and non-cash stock expenses.”

“In addition,” Grenfell-Gardner continued, “we have continued to advance our plan to start-up manufacturing of commercial product in our sterile injectable facility. We have recently con-

firmed with the US Food and Drug Administration (FDA) an expedited review pathway for the first injectable drug that will trigger FDA inspection of the site.”

Having commissioned its expanded US manufacturing facility in Buena, New Jersey, Teligent in the last quarter of 2018 began the process of transferring the manufacture of its semi-solid and liquid topical products into its new bulk-drug compounding suites. This includes completing the media fills for a number of aseptic sizes to support aseptic-filling capabilities in its sterile injectables suite.

INJECTABLES FACILITY IS COMING ONLINE During the fourth quarter of 2018 and the first quarter of 2019, the firm “added in incremental external experts to help us dou-ble- and triple-check our systems and provide incremental sup-port to our ongoing work”.

“I believe we are still on track to have the facility inspected by the US Food and Drug Administration (FDA) this year and for the first injectable product to be launched by the end of 2019,” Grenfell-Gardner contended as he presented 2018 financial re-sults in mid-March. “And that’s pretty exciting, particularly given the dynamics that we continue to see in the injectable markets.”

Triggering the audit in “the first half of this year” would en-able Teligent to launch products “in the back half” of 2019, he acknowledged.


Teligent's share price has fallen by almost a quarter in one month

From a closing price of $1.30 on 18 March this year, Teligent's share price has fallen by 23% to close at$1.00 on 15 April.

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Teligent's share price from 18 March 2019 to 15 April 2019 (Source - Teligent)

Teligent’s share price has fallen by almost a quarter in one monthFrom a closing price of $1.30 on 18 March this year, Teligent’s share price has fallen by 23% to close at $1.00 on 15 April.

Teligent’s share price from 18 March 2019 to 15 April 2019 (Source - Teligent)

ANALYZEFurther information related to this story is available here: https://bit.ly/2UuTZM4



B I O S I M I L A R S

Teva Gets Canadian Rituximab Nod, But Barriers May RemainAIDAN FRY [email protected]

T eva Canada and partner Cell-trion have received a notice of compliance (NOC), or marketing

authorization, from Health Canada for Truxima (rituximab), “the first biosimilar” to Roche’s Rituxan in Canada. But intel-lectual-property barriers could yet hold up Teva’s launch plans.

Health Canada NOCs granted to Cell-trion Healthcare’s 100mg/10ml and 500mg/50ml single-dose vials on 4 April list the approved indications as non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL) and rheu-matoid arthritis (RA). Rituxan for infu-sion is also indicated for granulomatosis with polyangiitis.

But Teva Canada, which is listed in the

NOCs as the local distributor, is keeping its cards close to its chest on when Trux-ima may offer competition to Rituxan in the Canadian market.

TERMS AND CONDITIONS FOR LAUNCH REMAIN CONFIDENTIAL

“At this moment, the terms and condi-tions regarding the plan following the NOC announcement in Canada, includ-ing launching time, remain confidential,” a spokesperson for Teva told Generics Bulletin. “The same policy of confidential-ity applies to any information related to entry terms,” she added.

Health Canada’s drugs patent register lists eight patents against Roche’s Ritux-an 10mg/ml solution for infusion, with expiry dates ranging between August 2019 and November 2026.

In 2017, Roche sued Celltrion over Truxima for alleged patent infringement through four proceedings under Cana-da’s Patented Medicines (Notice of Com-pliance), or PM(NOC), patent-linkage framework. Those actions concern Cana-dian patents:

• 2,340,091 that expires on 11 August 2019

• 2,350,058 that expires on 9 Novem-ber 2019

• 2,372,603 that expires on 4 May 2020• 2,378,574 that expires on 2 August 2020

• 2,783,210 that expires on 14 Novem-ber 2026

Four similar PM(NOC) cases brought by Roche against Sandoz’ Rixathon ritux-imab biosimilar candidate cite the ‘091, ‘058, ‘574 and ‘210 patents.

According to the Canadian agency for drugs and technologies in health (CADTH) reimbursement body, local sales of Rituxan reached C$241 million ($181 million) in 2016, ranking Roche’s brand seventh in terms of the best-selling bio-logic drugs in Canada.

Citing data showing a considerable Canadian market for rituximab, Teva not-ed that about 300,000, or one in every 100, Canadians had RA. Around 36,175 Canadians were living with NHL or were in remission, the firm noted, while 2013 data showed that, from an estimated 2,460 Canadians diagnosed with CLL, 608 had died of it.

The Israeli group said its rituximab ap-proval “establishes Teva’s position in the biosimilars space and leverages its exist-ing expertise in the oncology market”.

“Biosimilars are a new chapter in the therapeutic oncology setting in Canada and represent a growing focus for Teva since they will allow us to increase ac-cess to important therapeutic options,” commented Christine Poulin, senior vice-president and general manager

“Biosimilars are a new chapter in the therapeutic oncology setting in Canada and represent a growing focus for Teva since they will allow us to increase access to important therapeutic options”

“At this moment, the terms and conditions regarding the plan following the NOC announcement in Canada, including launching time, remain confidential”


B I O S I M I L A R S / L E G A L I S S U E S

of Teva Canada. “Moreover, Teva’s bio-similars will have the potential to reduce costs by providing lower-cost treatment options for patients.”

TRUXINA IS ALREADY APPROVED IN KOREA, EUROPE AND US

Soon after Teva and Celltrion in October 2016 entered into an exclusive deal for Truxima and Herzuma (trastuzumab) rights in North America, the South Ko-rean firm secured its first approval for Truxima in its domestic market. Europe-an Commission approval came in Feb-ruary 2017, and Truxima has since been launched in 26 European countries, in-cluding in France, Germany, Italy, the Netherlands and the UK. The EU autho-rization was followed by Food and Drug Administration clearance in the US in November 2018.

TEVA CANADA REPORTED SALES OF OVER $1BN IN 2017

Building on the heritage of its 2000 No-vopharm acquisition, Teva says its Toron-to-based Canadian operation generated a turnover of more than $1 billion in 2017 from filling around 250,000 prescriptions. Branded drugs such as oncology, central nervous system, pain and respiratory products are marketed through its Teva Canada Innovation division.

Teva Canada and Teva Canada In-novation have recently avoided being added as defendants in Roche’s federal court case against Celltrion Healthcare over the Korean company’s Herzuma biosimilar of Roche’s Herceptin breast-cancer treatment. Case management judge Mandy Aylen agreed to remove Canadian patent 2,376,596 from the litigation. Health Canada’s patent register also lists Canadian patents 2,407,556; 2,540,547; and 2,596,133 against Herceptin.


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UK Shortages Scheme Stands Up To Legal ScrutinyAIDAN FRY [email protected]

A Serious Shortage Protocol (SSP) that allows UK pharmacists to dis-pense a different medicine to that

prescribed so as to mitigate the effects of disruptions to supply of prescription drugs is legal, UK courts have decided. Generic substitution is currently not permitted in the UK, but doctors typically prescribe by international non-proprietary name (INN).

Administrative court judge Mr Justice Supperstone refused permission for the Good Law Project – a body that aims to “use the law to deliver a progressive so-ciety” – to challenge the insertion into the UK’s Human Medicines Regulations of a measure that permits ministers to issue an SSP if they believe the UK “is ex-periencing, or may experience, a serious shortage of a prescription-only medicine or prescription-only medicines”.

Under an SSP, a pharmacist could supply the patient with a different strength, quan-tity or pharmaceutical form of the medicine ordered by the doctor, or a medicine other than that prescribed. In the latter case this could be a generic version, a biosimilar (in-cluding a different biosimilar from the one prescribed), or a medicine that has “a similar therapeutic effect” to the one prescribed.

CHALLENGE CLAIMED PROCESS WAS RUSHED AND INADEQUATE

The Good Law Project had argued that the Secretary of State for Health and Social Care did not have the power to make the regula-tory change. And even if he did, “the process by which he made it was so rushed and in-adequate as to render it unlawful”. Patients, it claimed, had not been sufficiently involved in the decision amid “a failure to consult”.

UK industry body the British Generic Manufacturers Association (BGMA) has also expressed its concerns about giving pharmacists wide powers to dispense al-ternative medicines to those prescribed.

But Supperstone described the legisla-tive move as “plainly an important legis-lative measure designed to enable the Secretary of State effectively to address serious drug shortages, including any

potential drug shortages that may occur in the event of a no-deal Brexit” with-drawal from the European Union.

SSPs, the judge said, offered a “parallel system” to pharmacists dispensing pre-scriptions as written, and did not affect the classification of medicines as being available only by prescription.

Sufficient regard had been taken on whether the provision would affect spe-cific groups of patients, he decided. And the consultation exercise was “fair and adequate”, especially in light of “the time constraints involved” of ensuring the changes were in place by the 29 March 2019 date on which the UK was initially scheduled to leave the EU.

The Good Law Project – which describes Brexit as “a terrible idea” – had already in mid-March failed to persuade another High Court judge of the merit of its arguments.

Earlier this year, the BGMA’s director general, Warwick Smith, told Generics Bulletin that “the flexibilities put forward should only be capable of being applied in limited circumstances.”

“This would be the case of a ‘no-deal’ Brexit where government and industry have exhausted all other options to supply medicines to the UK market and there is an imminent and real risk of serious patient need not being met. This is a measure for only an extreme scenario and should not be enacted for more routine supply issues.”


“This is a measure for only an extreme scenario

and should not be enacted for more routine

supply issues”




Russia’s Generium Announces First Biosimilar Of Soliris PENELOPE MACRAE

Orphan-disease drug company Generium JSC, owned by Rus-sian billionaire Viktor Khari-

tonin, says it has launched the first biosimilar of Alexion’s blockbuster medicine Soliris (eculizumab) to treat two extremely rare and life-threatening blood diseases. The Russian biosimilar is branded under the name of Elizaria and was developed using a platform created by Switzerland-based cell-line develop-ment specialist Selexis SA.

“We’re the first company in the world to develop and market a biosimilar of eculi-zumab. It’s a great milestone for our compa-ny,” Vsevolod Letsko, a spokesman for Mos-cow-based Generium, told Generics Bulletin.

Generium, a leading Russian devel-oper of drugs to treat orphan diseases, says its biosimilar monoclonal antibody, eculizumab, is currently authorized to treat atypical hemolytic uremic syn-drome (aHUS) as well as for the treat-

ment of paroxysmal nocturnal hemo-globinuria (PNH). But Letsko said the authorization could be extended to treatment of other illnesses.

A progressive disease which frequently has a genetic component, aHUS is char-acterized by formation of blood clots that can cause strokes, heart attacks, kidney failure and death. Eculizumab significantly improves renal function in

patients with aHUS. PNH, meanwhile, is a disease characterized by destruction of red blood cells by the immune system. In people with PNH, eculizumab reduces both destruction of red blood cells and the need for blood transfusion.

Generium’s eculizumab is the first bio-similar challenger to emerge to Alexion’s Soliris, which has been a cash cow for the Boston-based company whose focus is on developing treatments for orphan diseases. Soliris, launched in 2007, ac-counted for more than 86% of the com-pany’s revenues in fiscal 2018, according to Alexion’s annual report.

SOLIRIS IS ONE OF THE MOST EXPENSIVE DRUGS GLOBALLY, ELIZARIA TO BE PRICED LOWER

Soliris, which got FDA approval in 2017 used to treat a muscle condition, gen-eralized myasthenia gravis, costs $6,830 for each 300mg vial. But patients require

more than one vial per dose. Solaris aver-ages around $18,000 per dose – delivered every two weeks – and this can cost at least $500,000 a year in the US, making it one of the world’s most costly drugs. Treatment is life-long. Generium spokesman Letsko said the company’s eculizumab, which has only been approved for Russia so far, will cost Rb248,000 ($3,853) per vial.

“The joint efforts of Russian, US and

Swiss scientists have made it possible to achieve significant progress in the devel-opment of high-tech medicines for the treatment of rare diseases such as a PNH and aHUS, with the economic benefits of local production,” said Generium’s chief executive Dmitriy Kudlay in a statement.

Generium is focused on developing and commercializing diagnostic systems and pharmaceutical products for treat-ing orphan diseases, infection diseases, cancer, multiple sclerosis, myocardial in-farction and strokes. Generium consists of a high-end R&D center and a fully inte-grated manufacturing plant.

Letsko said development of ecu-lizumab took more than five years. “We’ve got more than 30 other drugs in the development pipeline,” he added, saying that they include ones to treat cystic fibrosis, bronchial asthma, leu-kemia, cardiovascular disorders and macular degeneration.

Generium developed the drug us-ing Selexis’ SUREtechnology Platform is based on Selexis SGE pr Selexis Genetic Elements — novel human DNA-based elements that control the dynamic or-ganization of chromatin across mam-malian cells. SUREtechnology improves the way cells are used in the discovery, development and manufacturing of re-combinant proteins.

“This biologics market approval in Rus-sia represents another major milestone for Selexis… it becomes the fifth mar-keted product using the Selexis SURE technology platform,” Selexis company’s chief executive Igor Fisch said.. “There are currently more than 115 clinical pro-grams utilizing the SUREtechnology Plat-form, including nine Phase 3 programs. Selexis says its platform helps develop “complex protein therapeutics faster, safer and more cost efficiently.

Alexion recently announced it had obtained three new US patents cover-ing Soliris that will expire in 2027. But in January, the European Patent Office re-voked Alexion’s patents to extend Soliris



Sun Is Set Fair For Fenofibrate Entry In AustraliaAIDAN FRY [email protected]

S un Pharma can proceed with its plans to launch generic fenofibrate into Australia’s private prescription

market at the end of this month after an Australian federal court refused Mylan an injunction to prevent competition to its Lipidil treatment for high cholesterol and diabetic retinopathy.

Sun – which has offered to supply its fenofibrate generics at a 63% discount to the pharmacy purchase price of Lipi-dil – is lining up a move into the public fenofibrate market after it gets a Phar-maceutical Benefits Schedule (PBS) re-imbursement listing from 1 June, while Cipla plans to follow with a similar PBS clearance. Mylan intends to respond by introducing an authorized generic.

Having unsuccessfully sued Sun for al-leged infringement of Australian patents 2006,313,711 and 2003,301,807, Mylan had sought an interim injunction while it appealed against a finding that both patents were invalid. The ‘711 patent cov-ers the use of fenofibrate for preventing diabetic retinopathy and expires in No-

vember 2026; the ‘807 patent is entitled ‘Nanoparticulate fibrate formulations’ and expires in May 2023.

CIPLA AGREED TO TAKE PART IN INJUNCTION PROCEEDINGS

Shortly after seeking the injunction against Sun, Mylan sued Cipla for threat-ened infringement of the ‘711 patent and started to consider whether to also sue the Indian firm over the ‘807 patent. Cipla agreed to join the injunction proceedings.

Denying Mylan’s petition for an injunc-tion and awarding costs to Sun and Cipla, Justice David Yates noted that a judge in the main primary proceedings had re-cently found that the ‘711 method-of-use patent was invalid in light of an ‘Accord’ eye study protocol and the application for European patent EP0,482,498. The ‘807 patent was invalid for lacking an inventive step on the basis of common general knowledge and US patent ap-plication 2002/0012704 entitled ‘Water-insoluble drug particle process’.

Revocation orders against the two Aus-

“Mylan faces the significant hurdle that the primary judge found that the claims are invalid on two separate and independent bases – lack of novelty and lack of inventive step”

protection for all indications until 2027 in Europe following a challenge from US biopharmaceutical multinational Amgen Inc. which is looking to develop a biosim-ilar of eculizumab.

SOLARIS AIMS TO BUTTRESS PATENT SUPPORT OF SOLIRIS

Analysts say the EPO decision means bio-similars could start making inroads into sales of Soliris in Europe starting in 2022, although Alexion said on 21 January it ex-pects to appeal the ruling as well as pur-sue additional European patent filings in support of Soliris.

However, Alexion already has a next-generation version of Soliris, known as Ultomiris, which has got early FDA approval for treatment of PNH in the US and is under consideration in Ja-

pan and Europe. Alexion is also going to seek regulatory approval in the US, EU and Japan for Ultomiris for treating aHUS after it fared well in an aHUS piv-otal study.

Alexion said in an investor presenta-tion in March its “ambition is to convert more than 70% of patients to Ultomiris within two years of launch.” The advan-tage to Ultomiris is that it only needs to be given every eight weeks compared with every two weeks with Soliris. Alex-ion says it plans to price Ultomiris slight-ly lower than Soliris at $6,404 per vial.

Alexion’s 2019 guidance for Soliris and Ultomiris revenues range from $3.9bn-$4bn, out of total revenue guidance be-tween $4.6bn and $4.7bn.


“We’re the first company in the world to develop

and market a biosimilar of

eculizumab. It’s a great milestone for our company”





Rescue Plan For Debt-Laden Panacea Sees Shares SoarPENELOPE MACRAE

T he India Resurgence Fund, run by investment firm Bain Capital and Piramal Enterprises conglomerate,

has unveiled a $144m rescue package for debt-laden generics developer and vaccine-maker Panacea Biotec Ltd. which has been struggling to get back on its fi-nancial feet for nearly a decade.

The money is intended to provide a “one-time settlement to existing lenders,” supply working capital and help meet Panacea’s growth needs, the India Resurgence Fund or IndiaRF said in a statement. The invest-ment also will give the fund a 10.4% stake in Panacea. The company’s shares, which have underperformed in recent years, leapt nearly 19% on 9 April following the announcement before retreating on profit-taking to close up 10.65% at INR200.45.

IndiaRF, which invests in distressed as-

sets, is partnering with the company at a “critical juncture,” Panacea’s managing di-rector Rajesh Jain said. The company aims to leverage the fund’s “proven global ex-pertise in restructuring and turnarounds,” he added, expressing confidence that the combined efforts of Panacea and In-diaRF will “help accelerate our ambitious growth and profitability targets.

Panacea is working on a “robust pipeline” of high barrier-to-entry generics, leverag-ing its capabilities in nanotechnology and platform drug-delivery technologies like micro-particles, liposomes, gastroreten-tive systems. For example, last year the company partnered with Natco Pharma and Breckenridge to bring a generic of

Celgene’s Vidaza (azacitidine) to the US, with Panacea producing the inject-able drug at its facility in Baddi, India.

In addition, it has been seeking to expand its international exports business, particular-ly to the US, to diversify from over-reliance on the global vaccine tender market which can be erratic and is highly competitive.

The announcement of the rescue package follows news on 26 February that Panacea had struck a one-time settlement deal with lenders to pay off INR8.64bn worth of debt. Also, at an extraordinary general meeting a month later, shareholders gave manage-ment the green light to raise up to INR1.28bn via the issuance of preferential warrants.

IndiaRF invests debt and equity capital to help ailing firms in the Indian market, focusing on all sectors except real estate. The fund says it looks to put money in businesses whose balance sheets need restructuring but which also have “fun-damentally strong growth prospects”

tralian patents were stayed pending appeal.Sun had in February 2016 secured ap-

provals and entries on the Australian Register of Therapeutic Goods (ARTG) for 12 fenofibrate products under both Sun and Ranbaxy labels. These were initially approved for both reducing cholesterol and treating diabetic retinopathy, but Sun altered the labeling to delete the latter. In early May 2016, Mylan obtained an injunction against Sun launching that held until the primary proceedings deci-sion earlier this year.

Acknowledging that Mylan had “an arguable appeal” against the invalid-ity findings, Yates pointed out, however, that the company “faces the significant hurdle that the primary judge found that the claims are invalid on two separate and independent bases – lack of novelty and lack of inventive step”. Mylan would,

he said, need to prove that the primary judge was in error on both counts.

Weighing the balance of convenience for and against granting an injunction, Yates said it fell against granting relief to Mylan.

DIFFICULT TO CALCULATE DAMAGES FOR DETERED ENTRY

“If interim injunctive relief is granted and Mylan’s appeal fails, the task of assessing compensation would likely involve the consideration of multiple counterfactual cases advanced by multiple claimants,

including (I can anticipate) the Com-monwealth, each seeking to hypothesize what the market would have been like had interim injunctive relief not been granted,” he stated.

By contrast, Yates said it would be eas-ier to calculate damages due to Mylan if the patents were upheld on appeal. “In

assessing damages for infringement, the state of the market before generic entry, and at the time damages would come to be assessed, would be known and need not be hypothesized,” he argued.

There was, Yates believed, “a real pos-sibility” that Sun could realize its first-mover advantage, while Cipla, although not a first-mover, could also benefit from being among the first entrants with ge-neric fenofibrate.

“The preservation, to the extent pos-sible, of Sun Pharma’s possible ‘first mover’ advantage, and Cipla’s possible early mover advantage, must be seen in the context that there has been a full hearing on the validity of the relevant claims of the ‘711 patent and the ‘807 patent, and those claims have been found to be invalid,” Yates concluded. “So too must the interests of other third parties, such as other potential suppli-ers of generic fenofibrate products and the Commonwealth in relation to its op-eration of the PBS.”

Mylan’s appeal on the merits has been listed for case management on 6 May.


There was “a real possibility” that Sun could realize its first-mover advantage, while Cipla, although not a first-mover, could also benefit from being among the first entrants with generic fenofibrate

S T R AT E G Y


S T R AT E G Y

and whose exports are competitive.“The purpose of this investment is to not

only restructure the company’s balance sheet, but more importantly, work closely with the promoters and management team, to drive rapid revenue growth and sustainable profitability improvement,” the fund’s managing director Shantanu Nalavadi said. “IndiaRF continues to re-main focused on profitability,” he stressed, adding that the fund’s investment would help Panacea boost “its market position as a strong, research-focused pharmaceuti-cal and biotechnology company.”

STRUGGLING TO RECOVER FOR NEARLY A DECADE

Panacea has been struggling to get out of the red ever since it suffered a finan-cial body blow in 2011 when it lost World Health Organization prequalification sta-tus for a pentavalent vaccine Easyfive and two other vaccines over quality issues. That delisting sent the company into a financial tailspin. The delisting ended a couple of years later but Panacea is still fighting to get back to profit and owes tens of millions of dollars. The company entered a loan restructuring deal in 2014 but failed to make loan repayments.

In 2017, Panacea, which has some 3,000 employees, asserted that fiscal 2018-19 would mark the year that it would “bounce back.” But in its latest earnings statement in February, the company said for the three months to December 31, 2018, its net loss ballooned to INR230.2m from a net loss of INR97.1m in the same year-earlier period. Net sales slumped 25.18% to INR1.13bn in the third quarter year-on-year.

Panacea, which is among the top 15 pharmaceutical companies in its particu-lar biotech market segment, has some important firsts to its name. It pioneered in developing whole-cell (wP) based fully liquid combination vaccines and launched the world’s first fully liquid wP-IPV based TM hexavalent vaccine EasySix – diphtheria, whole cell pertussis, teta-nus, hepatitis B, Hib and IPV – and tetra-valent vaccine Easyfour-TT – diphtheria, whole-cell pertussis, tetanus and Hib. In January 2018 Panacea allied with the world’s largest-vaccine maker, the Serum Institute of India, to ramp up production of a six-in-one jab aimed at preventing killer diseases like polio and diphtheria

and target a global market estimated to be worth over $1.25bn annually.

Panacea’s portfolio includes products in areas from oncology, organ transplanta-tion, nephrology and diabetes to osteopo-rosis, cardiovascular diseases and pediatric vaccines. It said in its third-quarter earn-ings report it had taken a slew of perfor-mance-enhancing steps, including scaling up vaccine revenues, initiating supply of oral polio vaccine to different institutional buyers, striking strategic alliances with do-mestic and foreign collaborators to supply products, accelerating new product devel-opment and monetizing non-core assets.

PANACEA WARNED IN Q3 RESULTS STATEMENT ABOUT ABILITY TO ‘CONTINUE AS A GOING CONCERN’

Based on these efforts, “management believes it would be able to generate sus-tainable cash flow, recover and recoup the erosion of its net worth” and keep operating, Panacea said in the earnings statement. Still, the company also said continuous losses had “adversely affected” cash flows and warned of the possibility of “significant doubt about the company’s ability to continue as a going concern.”

IndiaRF’s Nalavadi said the fund’s mon-

ey would help Panacea “enhance its mar-ket position as a strong, research-focused” pharma and biotech company. The invest-ment will be structured as non-convert-ible debentures worth up to INR8.64bn. There will be a subscription amount of INR320m toward share warrants to be allotted preferentially. The subscription sum represents 25% of the total amount of INR1.28bn proposed to be raised upon the issuing of equity shares against war-rants. Subject to exercising the warrants, IndiaRF, along with its affiliates, will col-lectively end up owning a 10.4% stake in Panacea on a fully diluted basis.

Last October, billionaire industrialist and philanthropist Ajay Piramal, who is chairman of the $10bn Piramal Group, told India’s Economic Times newspaper that the IndiaRF totalled $300m. Piramal Enterprises, one of India’s large diversified companies with a presence in pharma, financial services and healthcare infor-mation and Bain Capital are committing $100m each to the fund while the Inter-national Finance Corporation, the World Bank’s private investment arm, has also in-vested $100m, according to the report.


“The purpose of this investment is to not only restructure the company’s balance sheet, but more importantly, work closely with the promoters and management team, to drive rapid revenue growth

and sustainable profitability improvement”



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