Biosimilars: Beyond the first product wave

Table of Contents

Foreword

Executive Summary

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

Products in the ‘first wave'

• 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
  • Sandoz
    • Hospira/Stada Arzneimittel
    • EPO zeta trial data published
    • Others in Europe
  • EMEA proposes tighter labelling for EPO products in cancer patients
  • 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
  • Saizen/Serostim
  • Bio-Tropin

• Current biosimilar activity
  • Current biosimilar activity in the USA
    • Accretropin receives FDA approval
  • Current biosimilar activity in the European Union
    • Biopartners makes Valtropin Phase III data available
  • Current biosimilar activity in the rest of the world
    • DEA action against Chinese HGH imports

CSF

• What is it?
• Who makes it?
• Developments on the Horizon
• Summary sales data
• Company specific sales data
  • Neupogen/Neulasta
  • Neutrogin/Granocyte
  • Leukine
• Current Biosimilar Activity
  • Current biosimilar activity in the USA
    • Teva to seek BLA for Tevagrastim in USA?
    • Hospira
    • Merck BioVentures
    • Apotex and Intas announce agreement to develop G-CSF
  • Current biosimilar activity in the European Union
    • Hospira submits EMEA application in Q109
    • CT, ratiopharm and Teva receive EU approval
    • Lithuania referred to European Court over Biosimilar G-CSF
  • Synageva Biopharma
  • 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
• Current biosimilar activity
  • Current biosimilar activity in the USA
  • Current biosimilar activity in the European Union
    • Marvel LifeSciences withdraws EU application
  • 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
    • Biopartners withdraws interferon beta application
  • Current biosimilar activity in the rest of the world

Beyond the first wave

• Etanercept
  • Summary sales data - Amgen (USA & Canada)
  • Summary sales data - Wyeth (Outside USA & Canada)
  • Current Biosimilar activity

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

Why are biosimilars an issue now?

• Rising cost of healthcare

Is there a commercially viable market?

• The price reduction of the biosimilar
  • Case Study: Biosimilar prices in the UK
    • Omnitrope
    • G-CSF
    • EPO
• Patient population
• Physician & patient acceptance
  • Attitudes to Biosimilars: UK Parliamentary Panel Reports
    • MHRA issues biosimilar prescribing guidance
    • Potential use of biosimilars in the NHS
    • Panel recommendations
  • HGH prescribing levels in England, 2008
• Regulatory attitude
• National pricing & reimbursement policies
  • Interchangeability and substitutability
• Extent of existing competition

• US surveys into cost savings
  • PCMA
  • Express Scripts
  • Avalere report
  • Insmed releases report on cost savings
  • CBO issues report on impact of biosimilars
  • Counter-arguments from BIO
  • President - s budget proposal, 2010
• Originator strategies to counter biosimilars
• Global market size estimates, 2015

The position in the USA

• Overview of the US regulatory system
• 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?
  • Current Moves in Congress, 2009
    • Promoting Innovation and Access to Life Saving Medicine Act (H.R. 1427/S. 726)
    • Pathway for Biosimilars Act (H.R. 1548)
    • Biologics Price Competition and Innovation Act (formerly S. 1695, now S. 1679, Title VI)
    • Interchangeability an option, not a requirement
    • Data exclusivity
    • Marketing exclusivity
    • Resolving patent disputes
  • Reaction from industry
  • Reaction from the White House
  • House Committee releases responses to biosimilar questionnaire
  • Data exclusivity
  • Interchangeability
  • Clinical trials
  • Should biosimilars have a separate INN?
  • FDA issue product class guidance?
  • Should the US follow the EU model?
  • Bio responds
• FDA Testimony to Congress, 2007
• FDA Briefing Paper issued, 2007
• Prospects for legislation in 2009

The position in Europe

• The new EU approval process
• Regulation of biosimilars
  • EMEA Guideline Documents
  • Current EU biosimilar approvals: somatropin
    • Omnitrope
    • Valtropin
    • BioPartners releases Phase III details for Valtropin
  • Current EU biosimilar approvals: EPO
    • Sandoz
    • Sandoz releases data for Binocrit
    • Stada/Hospira
    • Hospira presents trial data for Retacrit
  • Current EU biosimilar approvals: G-CSF
    • Sandoz
• Conclusions

The position elsewhere

• Other developed markets
  • Canada
    • Approval of Omnitrope
  • Australia and New Zealand
  • Japan
    • Approval of Omnitrope
  • Singapore
• Developing markets
  • Why are these markets worth a look?
    • India
    • Indonesia
    • Mexico
    • Saudi Arabia
    • Thailand

Who will be the players in the market?

• Manufacturer profiles
  • Abraxis BioScience
  • Anhui Anke Biotech
  • Avesthagen (Avestha Gengrane Technologies)
    • AVDESP trial gets go-ahead
    • BiotechCorp
    • Intas Pharmaceuticals
  • Bioclones
  • Biocon
    • Basalog
    • Insugen
    • Erypro
    • NUFIL
      • Abraxis and Biocon announce G-CSF partnership
    • Other products
    • Biocon buys majority stake in German marketing company
  • BioGeneriX
    • Merckle Biotech
    • Cangene
    • Neose Technologies
  • BioPartners
    • Valtropin
      • Sustained release HGH
    • Interferon applications rejected by EMEA
• Bioton S.A.
• Cangene
  • Accretropin
  • Leucotropin
• Cell Therapeutics
• Celltrion
• CIGB (Cuba)
• Cipla
  • Biomab
• CheilJedang (CJ Corp.)
• Cinnagen
• Claris Lifesciences
• Dr Reddy‘s
• Dongbao Biopharmaceutical
• Elona Biotechnologies
• GTC Biotherapeutics
  • AgResearch Ltd.
  • JCOM
  • LFB Biotechnologies
• Hospira
  • Distribution deal with Celltrion
  • Pliva sells biosimilar rights and facility to Hospira
  • Stada Arzneimittel
  • BresaGen
• Inno Biologics
• Intas Biopharmaceuticals
  • New MAB facility announced
  • Intas and Apotex sign G-CSF agreement
• Itero Biopharmaceuticals
• LG Life Sciences
• Marvel Lifesciences
• Merck BioVentures
  • Merck acquires Insmed - s biosimilar portfolio
• Momenta Pharmaceuticals
• NCPC Genetech
• Protalix Biotherapeutics
• Protein Production Services (PPS)
• Reliance Life Sciences
• Sandoz
  • Lek
  • Sandoz biotech plants, Austria
  • Lek biotech plant, Slovenia
• Selexis
• SciGen
  • Shreya Biotech
  • Chinese JV
  • Marketed Products
  • Pipeline Products
• Shantha Biotechnics
• 3SBio
  • EPIAO
  • Other products
  • Sales data
• Shenzhen Kexing Biotech
• Simcere
• Stada Arzneimittel
  • EPO-zeta gains EU approval
• Synageva Biopharma
• Teva Pharmaceuticals
  • G-CSF
    • Teva to seek BLA for Tevagrastim
  • Lonza
    • Lonza announces new Indian
  • Teva to divest Pliva - s biopharmaceutical
  • CoGenesys
  • Sicor Biotech UAB
    • Tianjin Hualida Biotechnology
• Three Rivers Pharmaceuticals
• Viropro
  • Deal with Intas Biopharmaceutical
  • Biochallenge agreement signed
• Wockhardt
• Zenotech Laboratories

Sources

Directory

• Regulators
• Industry Associations
• Manufacturers

Index

INDEX OF TABLES

• Leading EPO Brands, World Sales, 2001-2008 (US$ millions)
• Leading EPO Brands, % Change, 2002-08
• Leading EPO Brands, % of Subtotal, 2001-2008
• J&J Sales of Procrit/Eprex, 2001-2008 (US$ millions)
• Amgen Sales of Epogen/Aranesp, 2001-2008 (US$ millions)
• Amgen EPO Patents in the USA
• Roche Sales of Neorecormon/Epogin, 2002-2008 (SwF millions)
• Manufacturers' summary
• Leading HGH Brands, World Sales, 2001-2008 (US$ millions)
• Leading HGH Brands, % Change (US$ sales), 2002-08
• Leading HGH Brands, % of Subtotal, 2001-2008
• Genotropin Sales, 2001-08 (US$ millions)
• Humatrope Sales, 2001-08 (US$ millions)
• Novo Nordisk HGH Sales, 2001-08 (DKK millions)
• Genentech HGH Sales, 2001-08 (US$ millions)
• Merck/Serono HGH Sales, 2001-2008 (US$ millions)
• Manufacturers' Summary
• Leading G-CSF Brands, World Sales, 2001-2008 (US$ millions)
• Leading G-CSF Brands, % Change 2003-08
• Leading G-CSF Brands, % of Total, 2002-08
• Neupogen/Neulasta Sales, 2001-08 (US$ billions)
• Sales of Neutrogin/Granocyte, 2002-08 (billion yen)
• Manufacturers' Summary
• Leading Human Insulin brands, World Sales, 2001-2008 (US$ millions)
• Leading Human Insulin Brands, % Change, 2002-2008
• Leading Human Insulin Brands, % of Subtotal, 2001-2008
• Sales of Novo Nordisk Insulin Analogues, 2001-2008 (DKK million)
• Sales of Humulin and Humalog, 2001-2008 (US$000s)
• Lantus Sales by Region, 2004-08 (euro millions)
• Manufacturers' Summary
• Leading Interferon Brands, World Sales, 2001-2008 (US$ millions)
• Leading Interferon Brands, % of Subtotal, 2002-2008
• Sales of Intron A and PEG-Intron, 2002-2008 (US$ millions)
• Sales of Pegasys, 2002-08 (SwF millions)
• Sales of Betaseron/Betaferon, 2001-08 (euro millions)
• Sales of Avonex, 2001-08 (US$ millions)
• Sales of Rebif, 2001-08 (US$ millions)
• Manufacturers' Summary
• Summary, factors in favour of the development of biosimilars
• UK NHS Price Comparison, Omnitrope v other HGH Brands, 2008-09
• UK NHS Price Comparison, Ratiograstim v Neupogen, 2009
• UK NHS Price Comparison, EPO 2009
• Human Growth Hormone Prescriptions in England, 2008
• Anticipated Annual Savings to the Healthcare Budget from the Introduction of a Biosimilar Pathway, 2013-19 (US$ millions)
• Estimated Global Biosimilar Market Size (EPO, G-CSF and HGH), 2015 (US$ millions)
• FDA Response to Originator Arguments Against Omnitrope
• Omnitrope Phase III Trials Conducted In Support of NDA
• CHMP Guidelines, Drafts & Concept Papers
• Summary Requirements, Chemical Generic v Biosimilars
• Summary of Biosimilar Manufacturers and Products
• 2008 US$ exchange rates used in this report