applied strategic biosimilars success

applied strategic

10 years experience in biosimilars: launch to the future. What matters most?

Presentation by Dr Richard Littlewood

9 March 2016

8th Biosimilars Congregation

applied strategic 1

Analytics

What we all know? Definition of similarity concept for biologic medicines defined a new market for biosimilars

applied strategic 2

Preclinical

PK/PD

Clinical Trials

Process development

Source: McCamish 2011, CMHP/437/04

Biological Characterization

Physiochemical Characterization

“A company may choose to develop a new biological medicinal product claimed to be “similar” to a

reference medicinal product”

CHMP/437/04

What do we expect? Rapid growth to $35B global market for biosimilars, predicted by observers

applied strategic 3

Biosimilars global sales [2013-2020, $B]

60%

CAGR

Biosimilars

2013 2020

Biologics

175

285

Source: Merck Serono 2014, Blackstone & Joseph 2013, EGA 2015, Evaluate Group 2014

When did it start? Radical regulatory affairs innovation by EMEA, 2004 and key guidance launched biosimilars

applied strategic Source: applied strategic analysis EMA

Legal progress

Regulatory progress

2001 2002 2003 2004 2005 2006

Directive 2003/63/EC “Annex I” biosimiars

recognition

Directive 2004/27/EC published

Directive 2004/27/EC

in law

First biosimilar approved

Product guidelines

hGh, insulin, EPO, G-CSF

Comparability guidelines

Quality, non-clinical, clinical

guidelines

Where did it start? In Europe work started pre-2000; alternative biologics versions were marketed in LATAM also

applied strategic 5

Europe1998: Start development of

Binocrit® (epoetin alfa)

Mexico1999: launch of Bioyetin

(epoetin alfa)

Source: applied strategic analysis

What is the impact? Early product launches in Europe highlight commercial and patient access success

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• Launch of biosimilar Epoetin alfa in Europe

• 5 year healthcare cumulative savings to Germany, €0.6B

• Typically 35% cost reduction

• 255,000 patient-years exposure

Biosimilar Epoetin Alfa Launch 2007

Commercial & patient access success


What is the impact? A relatively small set of biosimilar products are currently marketed

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Omnitrope

Silapo

EpoHexal

Binocrit

Abseamed

Tevalgrastim

Ratiograstim

Biograstim

Retracrit

Nivestim

Remsima

Ovaleap

Inflectra

Grastofil

Bemfola

Accofil

Abasglar

Benepali

Zarzio

FilgrastimHexal

20162006 2011

Source: GaBI, Biosimilars approved in Europe 2016

European product approvals

What is the impact? Few companies own a majority of the assets: market looks an oligopoly…

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Omnitrope

Silapo

EpoHexal

Binocrit

Abseamed

Tevagrastim

Ratiograstim

Biograstim

Retracrit

Nivestim

Remsima

Ovaleap

Inflectra

Grastofil

Bemfola

Accofil

Abasglar

Benepali

Zarzio

FilgrastimHexal

20162006 2011

Source: GaBI, Biosimilars approved in Europe 2016

European product approvals

Assets owned by companies with portfolio of biosimiars

What is the future? Patent expiry, freedom to operate for many biologics defines a $B expansion of opportunity

Monoclonal antibodies approved/ under review in EU/ US [Patent expiry]

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<2020 >2020

Oncology

Non-on-cology

17

32


• 49 monoclonal antibody products have potential for biosimilar launch

• Launch of biosimilar versions of these products represents a step change in opportunity size

Potential value $20-30B

Expiry of patent, year

What is the future? New biosimilar products – based on antibodies – imply increasing manufacturing complexity

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Trade Name (INN) Originator Approval dateTysabri® (Natalizumab) Biogen Idec 2004Lucentis® (Ranibizumab) Roche/ Novartis 2006Cimzia® (Certolizumab) UCB 2009Stelara® (Ustekinumab) Johnson & Johnson 2009Eylea® (Aflibercept) Bayer/ Regeneron 2011Zaltrap® (Aflibercept) Sanofi/ Regeneron 2012Prolia®/Xgeva® (Denosumab) Amgen 2011Benlysta® (Belimumab) GlaxoSmithKline 2011Soliris® (Eculizumab) Alexion 2007, 2011


• Future products with potential to be biosimilars are based on antibodies• Greater manufacturing complexity, defining a special capability need

What is the future? Success with biosimilars is driving increasing simplicity in evidence needed for approval


“a confirmatory clinical trial may not be necessary”

EMA 2014

“waiving clinical trials may be accomplishable for biosimilar

rhG-CSF”

EMA 2015

“pre-licensing safety study, immunogenicity assessment

waived?

EMA 2015

“PK PD results may make a comparative efficacy study

unnecessary”

FDA 2015


What is the future? A broad range of competitors now are present: partners are a major part of the business


Merck Sorono, MerckPfizer, Daiichi-SankyoBoehringer Ingelheim,

biogen idecBaxter, Lilly, Amgen

Sandoz, TevaHospira, Mylan

STADA, Dr. Reddy’s, actavis. Cipla, Gideon

Richter

FujifilmSamsung

GE HealthcareCelltrion

Innovative companies

Genericsmanufacturers Others

BioconLonza

FormyconPatheon

IntasIBA Bioton

ZydusBroughton

ZydusWockhardt

CMCRentschler

Key partners: supporting development, contract development, manufacturers

Competitors: Commercializing biosimilar products


What drives success? First commercial phase. Success factors: protein characterization, regulatory affairs


Development Clinical Regulatory Launch Commercial

Cell line to product development; protein

characterization; comparability

Agency relationships, strategic leadership;

pathway interpretation

Tender management, pricing strategy.

Customer awareness

Customer awareness, defending against

restrictions;Policy management

Success Factors for Biosimilar Competition: First Commercial Phase (2006-2016)

What drives success? Next 10 years Success factors: commercial power, speed to market


Development Clinical Regulatory Launch Commercial

Complex protein manufacture

R&D partnerships

Capability to delivery clinical studies rapidly

Marketing & Sales power

Race to market

Success Factors for Biosimilar Competition: Second Commercial Phase (2017-2027)

Speaker profileDr. Richard Littlewood

• Richard is the founder of the strategy firm applied strategic

• is a physician with clinical practice experience and a management consultant who has worked for 15 years addressing strategic and operational issues in health, pharma

• He is a UK GMC registered physician, has an MA from Trinity College, Cambridge and is a graduate of the Sloan Masters management program at London Business School.

• Richard pioneered on biosimilars strategy and has extensive experience in many developed and emerging markets.

15

[appliedstrategic founder]

Dr. Richard Littlewood

• Adviser to global pharmaceutical companies involved in biosimilar development in Europe, USA and emerging markets since 2006

[Conflicts]