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patients • quality • value • sustainability • partnership

A Global View of Biosimilar Medicines

EU Experience (Part I)

The 2016 GPhA Biosimilars Council Conference 7-8 September 2016, Bethesda

Suzette Kox Senior Director International – Biosimilar Medicines Group

Chair IGBA Biosimilars Committee

COM

PAN

IES Biosimilar Medicines Group

Medicines for Europe Sector Group AS

SOCI

ATIO

NS


PARTNERSHIP

Vision 2020 - Our 5 pillars

3

PATIENTS M

edic

ines

for

Euro

pe V

ISIO

N

QUALITY

VALUE

SUSTAINABILITY


Outline

• Setting the US/EU scene and biosimilars potential • The European experience

• Regulatory & science • Market

• IMS observations • Biosimilar Medicines Group’s observations

• Simon-Kucher & Partners report • Payers’ P&MA policies supporting a sustainable biosimilar

market

Setting the Scene The economic case


Major social and economic challenges

6

Source: IMS Health, R&D Focus, May 2015; MIDAS, Q4 2014, constant USD

USD

Global spending on new brand medicines has more than doubled in 2014 and is 2.6% of global pharmaceutical spending

Global New Brand Spending Growth USD Bn


Biologics growth continues to put pressure on payers

-2%0%2%4%6%8%10%12%14%16%18%20%

05

101520253035404550

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

Gro

wth

, %

Sal

es,

€ bi

llions

BIOLOGIC MOLECULES Biologics growth Total Pharma growth

Source: IMS Health, MIDAS 2015

The size of biologic products losing patent exclusivity between 2015 and 2020 is significant

Source: IMS Health, MIDAS, Dec 2015

MAT

09/

2015

(BN

€)

Adalimumab Insulin glargine Etanercept Infliximab Rituximab Peg-filgrastim Trastuzumab Follitropin alfa

2018 2015 2016 2015 2016 2017 2018 2015 LOE

0,3

3,2 3,9

8,7

4,2 5,3

6,9

10,8 ES

USA UK FR

IT

DE

EU5+US Sales of Key Biologics Scheduled to Lose Patent Protection in 2015-2020

8 Delivering on the Potential of Biosimilar Medicines: The Role of Functioning Competitive Markets

If no competition, cumulative spending in the EU5 and the US is expected to reach $275 billion over the period 2016-2020

Notes: Addressable market is calculated based on projected growth of originator market without biosimiliar entry. Growth rate is based on historical growth and analogue analysis.

Conversion rate: 1 USD = 0.916562 EUR (01/20/2016)

100

250

0

200

150

50

199

246

2016-2020

25

5

15

40 35 30

10

50 45

20

0

17

5

2016-2020

DE

47

9 UK

FR 9

IT

ES

6

EU5

US

BN

€

BN

€

Source: IMS Health, MIDAS, IMS Health Market Prognosis, IMS Institute for Healthcare Informatics, Dec 2015

The Addressable Biosimilar Medicines Market in the EU5 and the US, 2016-2020


The cumulative savings over the next five years in the EU5 and the US combined could range from $55 billion to as much as $109 billion

Notes: Savings potential in EU5+US biosimilar accessible market dependent on change in price per treatment day. The accessible market analysis is based on Adalimumab, Insulin glargine, Etanercept, Infliximiab, Rituximab, Peg-filgrastim, Trastuzumab and Follitropin alpha. Savings potential in biosimilar accessible market at different price levels is calculated based on extrapolated size of the originator market between 2016 and 2020 based on historic CAGR and analogues. Accumulation of savings potential between 2016-2020 is shown

POTE

NTI

AL S

AVIN

GS

IN B

N€

100 90 80 70 60 50 40 30 20 10 0

2020 2019 2018 2017 2016

74

49

66

98

49

33 39

29 20 17 13 9

4 3 2

30% price reduction 40% price reduction 20% price reduction

Source: IMS Health, MIDAS, IMS Health Market Prognosis, IMS Institute for Healthcare Informatics, Dec 2015

Biosimilar Savings Potential in the EU5 and US, for 8 Key Products Going LOE in 2016-2020


At the end of 2015, there were some 41 biosimilar medicines in the pipeline for four key original biologics

SB2 (Samsung Bioepis)

GS071 (Aprogen)

Infliximab

PF-06438179 (Pfizer/Sandoz)

NI-071 (Nichiiko)

BOW15 (Epirus)

ABP 710 (Amgen)

BioXpress

Harvest Moon

Rituximab PF-05280586 (Pfizer)

CT-P10 (Celltrion)

GP2013 (Sandoz)

BI 695500 (BI)

ABP 798 (Amgen) MK-8808 (Merck)

Harvest Moon

BioXpress

AP052 (Aprogen)

MabionCD20 (Mabion)

Adalimumab

SB5 (Samsung)

ABP501 (Amgen)

Biocon

BI

GP2017 (Sandoz) FKB327 (Kyowa Kirin)

Oncobiologics

PF-06410293 (Pfizer)

LBAL (LG Life)

CHS-1420 (Coherus)

Harvest Moon

BioXpress

(BOW050) Epirus

M923 (Momenta)

Etanercept

CHS-0214 (Coherus) LBEC0101(LG Life)

Tunex (Mycenax ) GP2015 (Sandoz)

SB4 (Samsung Bioepis)

Biocon (PRX-106) Protalix

BioXpress

Avasthagen

Filed Late Phase Early Phase Preclinical

Source: IMS Health, IMS Institute for Healthcare Informatics, Jan 2016

Biosimilars in the Pipeline

11

The European Experience EU scientific and regulatory framework


Who decides what for biosimilar medicines in the EU?

13

Scientific assessment followed by scientific

opinion No interchangeability

designation

European Commission grants EU-wide marketing

authorisation

Member States: Price and

reimbursement, prescribing and

substitution policies


Guidelines are living documents

14

Overarching Guideline (CHMP/437/04) “Guideline on Similar Biological Medicinal Products”

Quality Guideline Non-clinical/clinical Guideline Revised

2014

Insulin Somatropin G-CSF Epoetin LMWH IFN-α IFN-β mAbs Follitropin

Class-specific Guidelines: non-clinical/clinical aspects:

General Guidelines:

2006 2006 2006 2006 2009 2009 2013 2012 2013

Revised 2014

Revised 2015

Revision ongoing

Revised 2015

Revised 2010

Revision ongoing

Revision ongoing

14 M. Weise, EBG Biosimilars 2016


EU scientific&regulatory framework ensures safe introduction and use of biosimilars

• Definition • version of the active substance of the reference product (RP) • comprehensive comparability exercise with the RP

• Same INN naming than RP

• RP label (less indications possible), product identified as biosimilar

• Extrapolation of indications • case-by-case, i.e. not automatic • based on the clinical experience with the RP and the entire similarity exercise i.e.

totality of evidence

• Risk Management Plan systematic; new PharmacoVigilance Module for biologics

• Identification and traceability: brand name + batch number


Consistent with biologics’ manufacturing changes: versions of same active; INN and label unchanged;

extrapolation applied

Vezér B, Buzás Zs, Sebeszta M, Zrubka Z.: Authorized manufacturing changes for therapeutic monoclonal antibodies (mAbs) in European Public Assessment Report (EPAR) documents. Curr Med Res Opin. 2016 May;32(5):829-34

433 manufacturing changes of 32 originator mAbs authorized by EMA (1998 -10/2014)


Identification of active substances is ensured

• The INN (International Nonproprietary Name) has always been the name for the active substance and was never intended to identify products on its own

• INNs should be granted on considerations of molecular characteristics and pharmacological class

• Comparability concept should be followed in order to ensure correct application of INN system

• No distinctive INN designation (connected or unconnected suffix) should be introduced to indicate a biosimilar product

• This approach is being successfully applied in Europe


Identification of medicinal products is also ensured

• Invented/Trade names identify products, and where unique product name is not mandatory, INN + corporate name allows clear identification • both options enshrined in EU legislation and a model for the world

• ISO IDMP (IDentification of Medicinal Products) standards have been developed and published in 2012 to establish a lasting international framework which allows exchange of medicinal product information in a robust and reliable manner and which supports interoperability across regulatory and healthcare communities • 10 years of intense work and international collaboration and rolled out now in the EU and

the US • unique identification of active substances part of ISO IDMP


WHO naming policy is confusing

• Proposed non memorable WHO BQ (Biological Qualifier) is • not necessary, • confusing • not developed according to ISO standards and hence not interoperable • is endangering the valuable INN system

• Resolution WHA46.19 on nonproprietary names for pharmaceutical substances requests Member States to “enact rules or regulations [...] to encourage manufacturers to rely on their corporate name and the international nonproprietary names [...] to promote and market multisource products introduced after the expiry of a patent“ • WHO INN guidance: http://www.who.int/medicines/services/inn/innguidance/en/

http://www.who.int/medicines/services/inn/innguidance/en/


In 10 years, move from science-based concept

to science and experience-based approach

EMA with its national experts have shaped biosimilar development and guidelines globally

Scientific & regulatory framework solidified by 10 years of safe and effective use of biosimilars in the EU and around the world

No unexpected side-effect identified

Increased tailoring and reduction of clinical programmes has become possible thanks to an increasing armamentarium and sensitivity of analytical tools

Further international convergence of data requirements is desirable to support true global development of biosimilars

The European Experience The market


21 biosimilar medicines approvals

Active substance Name of biosimilar Date of EC authorisation MA holder Reference product

Somatropin Omnitrope® 12-04-06 Sandoz Genotropin®

Epoetin

Abseamed® 28-08-07 Medice

Erypo® / Eprex®

Binocrit® 28-08-07 Sandoz

Epoetin alfa HEXAL® 28-08-07 Hexal

Retacrit® 18-12-07 Hospira

Silapo® 18-12-07 Stada

Filgrastim

Biograstim® 15-09-08 AbZ-Pharma

Neupogen®

Ratiograstim® 15-09-08 Ratiopharm

TevaGrastim® 15-09-08 Teva

Filgrastim HEXAL® 06-02-09 Hexal

Zarzio® 06-02-09 Sandoz

Nivestim® 08-06-10 Hospira

Grastofil® 18-10-13 Apotex

Accofil® 18-09-14 Accord Healthcare

Infliximab

Inflectra® 10-09-13 Hospira

Remicade® Remsima® 10-09-13 Celltrion

Flixabi® 26-05-16 Samsung Bioepis

Follitropin alfa Ovaleap® 27-09-13 Teva

Gonal f® Bemfola® 27-03-14 Finox Biotech

Insulin glargine Abasaglar® 09-09-14 Eli Lilly Lantus®

Etanercept Benepali® 18-01-16 Samsung Bioepis Enbrel®

Source: EMA (July 2016)


Uptake of biosimilar medicines varies by country and therapeutic area-Q1 2016

Source: IMS Health MIDAS Database Q1 2016

Biosimilar penetration of accessible markets

Some IMS Observations IMS report for the European Commission (data 2015)

Per Troein/VP Strategic Partners, IMS Health

IMS Health Biosimilar breif

Observation one: Competition drives down the price Prices before discounts and rebates

The increased competition affects not just the price for the directly comparable products but also the price of the

whole product class


Observation two: The correlation between biosimilars’ market share and price reduction is weak

• High savings can be achieved even if the share of biosimilars is low.

• Reduction can be achieved through price regulation and/or commercial decisions

• Biosimilar product s are likely an essential step to generate a competitive environment, which leads to price reduction


Observation three: Competition can also influence the originator’s behaviour

• Originators launching innovative long-acting/pegylated products without a price premium versus the short-acting, changing the treatment paradigm and therefore usage pattern

• Originators effectively reducing the price levels

• Originator companies are looking to launch biosimilar products

Insert Sweden


Observation four: Lower prices has the most impact on usage in countries with low initial usage

In countries which used to have low usage/availability in the classes the

price reductions seem to have a significant impact on the increased access.

2015

Biosimilar Medicines Group’s Observations


Biosimilar medicines – opportunity to meed unmet medical needs

In some European countries, patients have less access to biological treatments for Rheumatoid Arthritis (RA)

Sustainable biosimilar medicines market: • Patients • Prescribers • Pharmacists • Regulators • Payers • Industry

• ‘Sustainable policy framework’

A sustainable policy framework - Multi-stakeholder approach required


EC Consensus Information Document - Information and education remain key

• European Commission (EC) multi-stakeholder Information Consensus Document • available in 7 EU languages • new patient-friendly Q&A

• Annual multi-stakeholder biosimilars workshop

32


RWE: no evidence that switching leads to safety concerns

Review of switching studies of biological medicines (originator-originator or originator-biosimilar)

• Somatropin: 13 studies, 415 subjects (adults & children) • Epoetin: 35 studies, 11,249 subjects • Filgrastim: 10 studies, 374 subjects

Review 193 ADR reports for currently approved biosimilars • EPO – 46 • Filgrastim – 118 • Growth hormone – 29

No indication of safety issue resulting from switching between products No signal of switch-related adverse effects No data that switching induces increased immunogenicity

33 Ebbers et al. The safety of switching between therapeutic proteins. Expert Opinion on Biological Therapy 2012:12(11);1473-1485


Interchangeability under medical supervision supported by national authorities

• Medicines Evaluation Board – MEB (The Netherlands)1: Exchange between biological medicines (regardless of whether they are innovator

products or biosimilar medicinal products) is permitted, but only if adequate clinical monitoring is performed and the patient is properly informed.

• Finnish Medicines Agency – Fimea (Finland)2: Biosimilar medicines are interchangeable with their reference products under the

supervision of a health care person.

• Paul Ehrlich Institute – PEI (Germany)3: Biosimilars can be used in the same way as the reference products to which they have

shown equivalence. This implicitly covers both patients who have not yet received biological therapy as well as patients who previously received the originator molecule.

34

1 Are biosimilar medicines interchangeable? MEB position (2015). 2 Interchangeability of biosimilars – Position of Finnish Medicines Agency Fimea (22/2/2015). 3 Position of Paul-Ehrlich-Institute on interchangeability of biosimilar medicines (2015).

http://www.google.be/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://www.worldmapsinfo.com/flags/flag-of-germany.html&ei=3tcnVYf6NcqtsgHR3YCACg&bvm=bv.90491159,d.ZWU&psig=AFQjCNHbRIwOtSxWPpqWo9pI4AoimmlW8w&ust=1428760902209435

Position papers, accumulated experience & tenders to drive uptake

Payers have been instrumental in encouraging the use of biosimilar medicines


Sustainability of the biosimilar market

needs to be ensured

• Sustainability of the biosimilar market is a must to ensure that further long- term investments are made

• Simon-Kucher & Partners report to be published after mid-September 2016 • Payers’ P&MA policies supporting a sustainable biosimilar market

• High biosimilar penetration

• Payer guidance on biosimilars vs. originators

• Fair price level for biosimilars

• Commercial attractiveness

• Acknowledgement of high complexity of biosimilars within P&MA process

• Maintain healthy competition in the long-term

• Low effort needed to monitor and enforce policy

• Parallel sourcing from multiple manufacturers (short-term perspective)

• Earlier and broader use of biosimilars in additional patient segments

Criteria for an ideal sustainable biosimilar market to be developed


Principles for price & market access policies Simon-Kucher & Partners report

• P&MA policies should ensure a continuous market participation of several biosimilar manufacturers in order to maintain healthy competition • Example DE: Pharmadialog (agreement between industry and payers/policy makers)

• P&MA policies enforcing lower biosimilar prices compared to their originators have to be accompanied by specific guidance on biosimilar use and prescribing incentives. A lower price for biosimilars on its own will prevent generation of return on investments for biosimilar manufacturers

• A P&MA policy that does not allow for commercial attractiveness for biosimilar manufacturers will reduce competition in the long run and thus negatively impact the likelihood for payers to generate savings

• Gain sharing has proven to be a successful driver of biosimilar uptake across multiple markets, with benefits for both prescribers / decision makers and payers • Gain sharing is most effective in case the healthcare provider sees tangible benefits from

generated savings (additional services for patients, improved working conditions, monetary benefits, etc.)


Thank you and to my colleague Pieter Dylst

Questions?

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