(sandoz介绍生物类似药开发策略)Martin Schiestl

“Non-Comparable biologics” – not approved in highly regulated markets – are NOT biosimilars
Isoelectric focusing gels Alternative Epoetins ≠ biosimilar
Brockmeyer C & Seidl A et al. Eur J Hosp Pharm Pract 2009;15:34–40
4 | AHC Biosimilars Workshop, Seoul, April 2012, Martin Schiestl
Innovation required in both Technical Development and Clinical Development
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Why global biosimilar development?
Scientific principles allow global biosimilar development
Cost efficient Careful use of resources
Avoid unnecessary duplication of clinical trials
Global development of biosimilar products
Dr. Martin Schiestl
Scientific and Regulatory Advisor Sandoz GmbH
2012 APEC Harmonization Center Biosimilars Workshop, April 3-5, 2012
Байду номын сангаас
Agenda
Introduction
Why global biosimilar development? Considerations
• Regulatory framework
• Quality (API and drug product) • Clinical
Vision for an efficient pathway for a global biosimilar development
global scale in different regions • Extrapolate comparability package established in one region to the other regions
7 | AHC Biosimilars Workshop, Seoul, April 2012, Martin Schiestl
Procedural concern
• Access of the regulatory authority to information needed
• To be addressed by, e.g.
– Global programs for information and work sharing – Regulatory harmonization initiatives
Maximum positive health economic impact Foster global harmonization in pharmaceutical regulation in general
8 | AHC Biosimilars Workshop, Seoul, April 2012, Martin Schiestl
Global biosimilar development
Development of a biosimilar products for global markets
Utilize the fact that the originator markets the reference product on a
Define target Understand reference product Development of Manufacturing process Target directed approach Confirmation: Final comparability exercise of biosimilar candidate and reference product
Sandoz’ biosimilars are successfully marketed in 33+ countries No safety issues – same risk-benefit ratio as the reference products
3 | AHC Biosimilars Workshop, Seoul, April 2012, Martin Schiestl
NOT similar to Reference E
Approved biosimilar Epoetin alfa in EU
Highly similar to originator
Sample E IA IB IIA IIB IIIA IIIB IV
V VII VIII E
Sample
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2
3
4
Schellekens H et al. Eur J Hosp Pharm Pract 2004;3:43–7
100% = $380m
Other
11%
20%
48%
22%
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Sales of biosimilar products in regulated markets (EU/US/Australia/Japan/Canada); Other includes: Medice sales incremental to Sandoz Medice sales, and Stada / CT Arzneimittel. Source: IMS, Company reports, Sandoz assumptions 2 Source: “The Future of Biosimilars – Market Forecast to 2015,” GBI Research, Dec 2009; Internal Sandoz estimates 6 | AHC Biosimilars Workshop, Seoul, April 2012, Martin Schiestl
Japan regulatory guidelines Sandoz Somatropin first biosimilar approved and launched in Japan & Canada
WHO Biosimilar guidelines adopted
US Biosimilar guidelines drafted
Technical Development
Clinical Development
5 | AHC Biosimilars Workshop, Seoul, April 2012, Martin Schiestl
Sandoz biosimilars has ~50% market share
Highly regulated 2010 biosimilars market1 % Market share Future biosimilars market USD 2-3bn by 20152 USD 20+bn by 2020
2004
2005
2006
2007
2009
2010
2012
Sandoz Somatropin first biosimilar – type medicine approved in Australia
Sandoz Somatropin first biosimilartype medicine approved in US
Formal hurdles may continually be turned down in the future as
regulatory processes follow science
• Example: Current discussion in EU on circumstances that allow the use of a reference product sourced outside the EU
EU draft general guidelines adopted Sandoz Somatropin first biosimilar approved in EU Sandoz first EPO approved and in EU Sandoz Filgrastim approved in EU EU Draft mAb guidelines
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Important points to consider
Regulatory framework
• Regional biosimilar guidelines
Quality considerations
• Is the reference product marketed in all regions?
10 | AHC Biosimilars Workshop, Seoul, April 2012, Martin Schiestl
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Regional biosimilar guidelines show a high degree of harmonization
• Basic concepts in regulatory guidelines are the same already in many regions; e.g. WHO, JP, EU, US, Korea, Malaysia, Singapore
• Medical practice • Ethnic sensitivity
9 | AHC Biosimilars Workshop, Seoul, April 2012, Martin Schiestl
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Regulatory framework
Some regulatory flexibility available in some regions but not in all
• Are there any differences in the active pharmaceutical ingredient? • Are there differences in the presentation of the drug product?
Clinical considerations
Similarity at analytical level allows targeted preclinical and clinical program
Key challenges Time & Investment • Significant expense (USD 75 - 250m)
• Long time to develop (7-8 years)
• Achieving “highly similar” to match originator molecule profile • Matching final dosage form of originator • Use of novel endpoints and populations to confirm biosimilarity (not de novo safety/efficacy) • Clinical trial design to support extrapolation across indications, interchangeability & commercial success
Conclusion
2 | AHC Biosimilars Workshop, Seoul, April 2012, Martin Schiestl
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Biosimilars are recognized around the world as safe and effective medicines