世界のバイオシミラー医薬品市場

Abstract

Despite the lack of progress in the regulatory situation in the US, the biosimilars sector is forging ahead as generic companies gain ground in this high-reward/high-risk business.

The future of the pharmaceutical industry lies with biotechnology. Biotech drugs account for around 10-15% of the current pharmaceutical market, and the sector is outperforming the market as a whole in terms of growth.

The issue of the manufacture, approval and marketing of generic biotechnology drugs has become a major source of debate within the industry for two main reasons:

1. Cost containment. Biotech products are expensive to develop, manufacture and administer, and becoming more expensive as newer, more complex treatments are developed. The availability of generics would spur competition and hopefully reduce prices.

2. Patent expiry. Patents in the USA and Europe on the older biotech drugs have either expired or will begin to expire over the next few years.

Manufacturers in Asian, Eastern European and Latin American markets have been selling biologicals for years. But it is the valuable Western markets that excite, and a number of new approvals in the EU are raising interest in the biosimilar sector.

And it' s not just geographical expansion. Dr Reddy' s have launched a biosimilar version of rituximab for the Indian market, the first monoclonal antibody to be so produced.

The market may be developing but questions remain:

• Will a significant biosimilar market develop?
• Could an abridged regulatory process really benefit generic manufacturers?
• Which companies are making the moves that are driving change?
• Which therapies are now on the biosimilar radar?

Table of Contents

Foreword

Executive Summary

• What is a biologic drug?
• What' s in a name?
• Why are Biosimilars an issue?

The current state of the market for each of the major products

• Erythropoietin (Epoetin, EPO)
  • What is it?
  • Who makes it?
  • Developments on the Horizon
    • Mircera
      • EU Approval for Mircera
      • Dynepo
  • Summary sales data
  • Company-specific sales data
    • Procrit/Eprex
    • Epogen/Aranesp
    • Neorecormon/Epogin
  • Current biosimilar activity
    • Current biosimilar activity in the USA
    • Current biosimilar activity in the EU
    • Current biosimilar activity in the rest of the world
• Human Growth Hormone (somatropin)
  • What is it?
  • Who makes it?
  • Developments on the Horizon
  • Summary Sales data
  • Company specific sales data
    • Genotropin
    • Humatrope
    • Norditropin/other Novo Nordisk HGH products
    • Nutropin/other Genentech HGH products
    • Saizen/Serostim
    • Bio-Tropin
  • Current biosimilar activity
    • Current biosimilar activity in the USA
      • Accretropin
    • Current biosimilar activity in the European Union
    • Current biosimilar activity in the rest of the world
    • DEA action against Chinese HGH imports
• G-CSF
  • What is it?
  • Who makes it?
  • Developments of the Horizon
  • Summary Sales data
  • Company specific sales data
    • Neupogen/Neulasta
    • Neutrogin/Granocyte
    • Leukine
  • Current Biosimilar Activity
    • Current biosimilar activity in the USA
    • Current biosimilar activity in the European Union
    • Current biosimilar activity in the rest of the world
• Human Insulin
  • What is it?
  • Who makes it?
  • Summary Sales data
  • Company specific sales data
    • Novo Nordisk recombinant insulin products
    • Aventis recombinant insulin products: Lantus, Apidra
    • Pfizer: Exubera, inhaled insulin
  • Current biosimilar activity
    • Current biosimilar activity in the USA
    • Current biosimilar activity in the European Union
    • Current biosimilar activity in the rest of the world
• Interferon
  • What is it?
  • Who makes it?
  • Summary Sales data
  • Company specific sales data
    • Schering Plough Interferon A (Intron A range)
    • Betaseron/Betaferon
    • Rebif
  • Current Biosimilar Activity
    • Current biosimilar activity in the USA
    • Current biosimilar activity in the European Union
      • EMEA rejects Biopartners' Interferon A application
      • EMEA issues concept paper for biosimilar Interferon A
      • Biopartners submits Interferon beta to EMEA
    • Current biosimilar activity in the rest of the world

Beyond the First wave

• Monoclonal Antibodies
  • Rituximab
    • Summary sales data
    • Current Biosimilar activity
      • Dr Reddy' s
      • GTC Biotherapeutics/LFB

Factors in favour

• Rising cost of healthcare
  • US pharmaceutical expenditure increases

Factors against

• Science
  • The INN naming issue
    • EBE-EFPIA position paper on naming of biosimilars
    • Response from the generic industry
  • USP publishes monographs on somatropin
  • No strict definition of a biologic
• High cost of development and marketing
  • Product complexity
    • Will manufacturers have sufficient capacity?
  • Detail of regulatory requirements
    • Different international requirements
  • Postmarket surveillance requirements.
  • Marketing requirements
• Regulatory obstacles
  • US pathway still a long way off
    • What does the FDA really think?
• Legal problems
  • Patent challenges
  • Exclusivity of test data
• Product acceptance
  • Interchangeability and substitutability
  • Does biosimilar = obsolete?
  • Is there even a viable market?
    • Just what will the savings from biosimilars be?
      • PCMA
      • Express Scripts
      • Avalere report
      • BIO responds
  • Originator Strategies to Combat Biosimilars

The position in the USA

• Hatch-Waxman is not applicable to biologics
  • Exceptions
  • FDA transfer of biologic responsibility to CDER
• How feasible is the 505(b)(2) route ?
• Omnitrope in the USA
  • The FDA' s reasoning
  • FDA Response to Citizen Petitions regarding Omnitrope
  • The Scope of Clinical Trials Required for FDA Approval of Omnitrope
  • Conclusions regarding the FDA' s approval of Omnitrope:
• Easier not to seek an abridged application?
• Moves in Congress: BCPIA 2007
  • Interchangeability an option, not a requirement
  • Data exclusivity
  • Marketing exclusivity
  • Resolving patent disputes
  • Reactions
  • Biosimilars bills introduced in the House
  • Henry Waxman addresses criticisms
  • Bill criticised by the White House
  • Alternative bill introduced in the House
  • What happens next?
• FDA Testimony to Congress
• State Governors urges FDA to publish guidance, August 2006
• FDA Briefing Paper issued
• Conclusion

The position in Europe

• The new EU approval process
• Regulation of biosimilars
  • EMEA Guideline Documents
    • EPO
    • G-CSF
    • Somatropin
    • rH Insulin
    • Interferon alfa
  • The first EU biosimilar approvals: somatropin
    • Omnitrope
    • Omnitrope listed in the UK BNF
    • Valtropin
    • BioPartners releases Phase III details for Valtropin
  • Sandoz receives EPO approvals, 2007
• Conclusions

The position elsewhere

• Other developed markets
  • Australia and New Zealand
  • Japan
• Developing markets
  • Why are these markets worth a look?

Who will be the players in the market?

• Manufacturer profiles
  • Anhui Anke Biotech
  • Barr Pharmaceuticals
    • Pliva agreement for G-CSF
  • Biocon
  • BioGeneriX
    • Merckle Biotech
    • Cangene
    • Neose Technologies
  • BioPartners
  • Bioton S.A.
  • Cangene
  • Cell Therapeutics
  • CIGB (Cuba)
  • Cipla
  • CheilJedang (CJ Corp)
  • Dr Reddy' s
  • Dongbao Pharmaceutical
  • Dragon Pharmaceuticals
    • Merger with Oriental Wave Holdings
    • EPO
    • G-CSF
    • Sales data
  • GeneMedix
    • RLS acquisition
  • GeneScience Pharmaceuticals
  • Hospira
    • Mayne Pharma
    • Stada Arzneimittel
    • BresaGen
  • Inno Biologics
  • Intas Biopharmaceuticals
  • LG Life Sciences
  • Momenta Pharmaceuticals
    • New deal with Sandoz announced
  • NCPC Genetech
  • Pliva
    • EPO, Croatian approval granted
    • G-CSF, agreement with Barr Laboratories
    • Mayne Pharma
    • New biotech facility announced
  • Ranbaxy
    • G-CSF Agreement with Zenotech
  • Sandoz
    • Lek
    • Sandoz biotech plants, Austria
    • Lek biotech plant, Slovenia
  • SciGen
    • Shreya Biotech
    • Chinese JV
    • Marketed Products
    • Pipeline Products
  • 3SBio
    • EPIAO
    • Other products
    • Sales data
  • Shenzhen Kexing Biotech
  • Stada Arzneimittel
    • EPO submitted to EMEA
    • Plans for interferon b dropped
    • EPO distribution agreement signed with Hospira
  • Teva Pharmaceuticals
    • Tev Tropin
    • Sicor
    • Tianjin Hualida Biotechnology Pharmaceutical Co
  • Viropro
    • Deal with Intas Biopharmaceutical
    • Biochallenge agreement signed
  • Wockhardt
  • Zenotech Laboratories

Conclusions

Sources

Directory

• Regulators
• Industry Associations
• Manufacturers

INDEX OF TABLES

• Leading EPO Brands, World Sales, 2001-2006 (US$ millions)
• Leading EPO Brands, % Change, 2002-06
• Leading EPO Brands, % of Subtotal, 2001-2006
• J&J Sales of Procrit/Eprex, 2001-2006 (US$ millions)
• Amgen Sales of Epogen/Aranesp, 2001-2006 (US$ millions)
• Amgen EPO Patents in the USA
• Roche Sales of Neorecormon/Epogin, 2002-2006 (SwF millions)
• Manufacturers' summary
• Leading HGH Brands, World Sales, 2001-2006 (US$ millions)
• Leading HGH Brands, % Change, 2002-06
• Leading HGH Brands, % of Subtotal, 2001-2006
• Genotropin Sales, 2001-06 (US$ millions)
• Humatrope Sales, 2001-06 (US$ millions)
• Novo Nordisk HGH Sales, 2001-06 (DKK millions)
• Genentech HGH Sales, 2001-06 (US$ millions)
• Serono HGH Sales, 2001-2006 (US$ millions)
• Manufacturers' Summary
• Leading G-CSF Brands, World Sales, 2001-2006 (US$ millions)
• Leading G-CSF Brands, % Change 2003-06
• Leading G-CSF Brands, % of Total, 2002-06
• Neupogen/Neulasta Sales, 2001-06 (US$ billions)
• Sales of Neutrogin/Granocyte, 2002-06 (billion yen)
• Manufacturers' Summary
• Leading Human Insulin brands, World Sales, 2001-2006 (US$ millions)
• Leading Human Insulin Brands, % Change, 2002-2006
• Leading Human Insulin Brands, % of Subtotal, 2001-2006
• Sales of Novo Nordisk Insulin Analogues, 2001-2006 (DKK million)
• Sales of Humulin and Humalog, 2001-2006 (US$000s)
• Lantus Sales by Region, 2004-06 (euro millions)
• Manufacturers' Summary
• Leading Interferon Brands, World Sales, 2001-2006 (US$ millions)
• Leading Interferon Brands, % of Subtotal, 2002-2006
• Sales of Intron A and PEG-Intron, 2002-2006 (US$ millions)
• Sales of Pegasys, 2002-06 (SwF millions)
• Sales of Betaseron/Betaferon, 2001-06 (euro millions)
• Sales of Avonex, 2001-06 (US$ millions)
• Sales of Rebif, 2001-06 (US$ millions)
• Manufacturers' Summary
• Summary, factors in favour of the development of biosimilars
• US Research-Based Pharmaceutical Manufacturers' Sales, 1990-2006 (US$ millions)
• US Pharmaceutical Expenditure as % of GDP, 1990-2006
• Growth of Medicaid Pharmaceutical Expenditure, 1997-2005 (US$ millions)
• FDA Response to Originator Arguments Against Omnitrope
• Omnitrope Phase III Trials Conducted In Support of NDA
• Adopted Guidelines
• Documents submitted for ongoing comment
• CHMP Concept Papers, 2006
• Summary Requirements, Chemical Generic v Biosimilars
• Summary of Biosimilar Manufacturers and Products
• Dragon Pharmaceutical revenues by Segment, 2006 (US$ millions)
• 2006 US$ exchange rates used in this report