Biosimilars: another milestone passed

At the end of June 2013, the European Medicines Agency’s Committee for Medical Products for Human Use issued a positive opinion for the first biosimilar version of Johnson & Johnson’s infliximab for the treatment of rheumatoid arthritis, inflammatory bowel disease and plaque psoriasis. For the two successful applicants, Celltrion and Hospira, this development passes a significant milestone for the whole biosimilar sector as the products are the first monoclonal antibody (mAb) therapies to reach a positive opinion following review via the EMA biosimilars regulatory pathway. This is an important event which heralds a new era of lower-cost biological therapies in Europe.

For J&J and its partners, the news is less welcome. Already under pressure from branded competitors in the TNF inhibitor market, it is no surprise that both developer and biosimilar companies will be assessing what share they may secure of its US$6.13 billion revenues.

The tip of a US$41 billion iceberg

While significant for J&J, infliximab is just the tip of the iceberg when it comes to the potential for biosimilars. In terms of revenue, six of the top ten pharmaceutical therapies are biological products, which have been targeted by biosimilar developers: Abbvie’s Humira (adalimumab), Roche’s MabThera (rituximab), Herceptin (trastuzumab) and Avastin (bevacizumab), Sanofi’s Lantus (insulin glargine), and Johnson & Johnson’s Remicade (infliximab). These products had combined global sales of US$41.4 billion in 2012. Also of significant importance to biosimilar developers, with sales of US$4.2 billion in 2012 is Amgen’s Enbrel (etanercept).

Open season: Branded industry gets in on the act

It may have taken a while, but the world’s major pharmaceutical originators have recognised the potential for biosimilars. A number have disclosed their intentions and/or announced clinical trials in recent months. For example, in February 2013, Amgen announced plans to launch a portfolio of six new biosimilars beginning in 2017: adalimumab, infliximab, bevacizumab, trastuzumab, rituximab and cetuximab. Four of these projects form part of the  company’s development agreement with Actavis. In June 2012, Merck KGaA and Dr Reddy's Laboratories announced a partnership to co-develop a portfolio of biosimilar compounds in oncology, primarily focused on monoclonal antibodies. Pfizer has been openly active in generics and biosimilars for some time. The company previously had a collaborative deal with Biocon for its insulin products, although this deal was concluded in March 2012. In May 2013, Pfizer began a Phase I trial with an infliximab biosimilar, PF-06438179. Many smaller biosimilar developers have the ambition but not the resources. The increasing interest from big Pharma will bring a welcome boost of expertise and funding to research and partnering.

The US Market: Not the elephant in the room

In any analysis of the pharma industry the US looms large – but not in biosimilars. The painfully slow progress to a regulatory pathway for biosimilars – still untried – has handed the initiative to others. The EU biosimilar regulations have been imitated widely in other countries, while the emphasis of biosimilar research sits firmly in Asia, notably India, China and South Korea. Of course, the big prize for all biosimilar manufacturers is the US market, which accounts for approximately 50% of the global value.

This report answers key questions:
  • Where is less competition to be found in the first phase of biosimilars in Epoetin and G-CSF?
  • Biosimilars are more widely available in emerging markets – what lessons can be learnt?
  • What are the latest State regulatory developments in the US and will they help or hinder?
  • Which are the companies to watch, and why?
  • Six companies are targeting Abbvie’s Humira, who are they and what is the status of their research?

Foreword & Executive Summary
  • Biosimilars: What Are They and Why Are We Interested?
  • What Is A Biotech Drug?
  • Biosimilars and Biobetters Defined Product Analysis Each product review which follows covers,where appropriate,
  • Developer/Background
  • Mode of Action
  • Approvals
  • Competition within the Marketplace
  • Patents
  • Sales Trends
    First Generation Biosimilars
  • Epogen/Eprex/Procrit (epoetin alfa)
  • Aranesp (darbepoetin alfa)
  • NeoRecormon (epoetin beta) Mircera (methoxy polyethylene glycolepoetin beta)
  • Biosimilar Erythropoietin
    ≫≫ Europe
  • ≫≫ USA
  • ≫≫ Rest of the World

    (Epoetin & Darbepoetin)G-CSF
  • Neupogen (filgrastim)
  • Neulasta (pegfilgrastim)
  • Neutrogin/Granocyte (lenograstim)
  • Biosimilar G-CSF
    ≫≫ Europe (Filgrastim andPegfilgrastim)
    ≫≫ USA
    ≫≫ Rest of the World

    Human Growth Hormone (Somatropin)

  • Genotropin
  • Humatrope
  • Norditropin
  • Nutropin
  • Saizen
  • Biosimilar Somatropin
≫≫ Europe
≫≫ USA
≫≫ Rest of the World

Follicle Stimulating Hormone
• Gonal-f (follitropin alfa)
• Biosimilar Follitropin Alfa
≫≫ Europe
≫≫ USA
≫≫ Rest of the World

Human Insulin

• Humulin (insulin [rDNA origin])
• Humalog (insulin lispro)
• Lantus (insulin glargine)
• Apidra (insulin glulisine)
• Levemir (insulin detemir)
• NovoRapid & NovoMix (insulin aspart)
• Biosimilar Human Insulin
≫≫ Europe and USA
≫≫ Rest of the World
• PegIntron (peginterferon alfa-2b)
• Pegasys (pegylated-40K interferon
• Avonex (interferon beta-1a)
• Rebif (interferon beta-1a)
• Betaferon/Betaseron & Extavia
(interferon beta-1b)
• Biosimilar Interferon
≫≫ Europe
≫≫ Rest of the World
The Next Biosimilar Generation:
Etanercept and Monoclonal Antibodies
• Enbrel (etanercept)
• Biosimilar Etanercept
• Remicade (infliximab)
• Rituxan/MabThera (rituximab)
• Herceptin (trastuzumab)
• Humira (adalimumab)
• Avastin (bevacizumab)
• Erbitux (cetuximab)

Biosimilar mAb Development
• Adalimumab
• Bevacizumab
• Cetuximab
• Infliximab
• Rituximab
• Trastuzumab
• Multiple mAb Development

≫≫ Oncobiologics Biosimilar

Biosimilar Regulation
• European Union
• United States

Regulation in Other Developed Markets

• Australia
• Canada
• Japan
• Singapore

Regulation in Emerging Markets
• Brazil
• India
• Malaysia
• Mexico
• Peru
• South Korea
• Turkey

The Key Players
• Sandoz
• Teva
• Hospira
Companies to Watch
• Actavis
• Biocon and Mylan
• Celltrion
• Ranbaxy
Major Pharma Companies – Recent Developments
• Amgen
• Merck & Co and Samsung Bioepis
• Merck Serono and Dr Reddy’s
• Pfizer
• Sanofi
Company Directory List of Tables
• Biosimilars Approved in the EU
• Five-year Sales of Leading EPO Brands (US$ M)
• Epogen US Patents
• Epogen/Eprex/Procrit Sales, 2003-2012 (US$ M)
• Aranesp US & EU Patents
• Aranesp Sales, 2003-2012 (US$ M)
• NeoRecormon/Epogin Sales, 2003-2012 (CHF & US$ M)
• Mircera Sales, 2003-2012 (CHF & US$ M)
• EU Marketing Authorisations for Biosimilar Eprex
• Biosimilar Epoetin in Emerging Markets
• Five-year Sales of Leading G-CSF Brands (US$ M)
• Filgrastim US Patents
• Neupogen Sales, 2003-2012 (US$ M)
• Pegfilgrastim Patents
• Neulasta Sales, 2003-2012 (US$ M)
• Neutrogin/Granocyte Sales, 2003-2012 (CHF & US$ M)
• EU Marketing Authorisations for Biosimilar Filgrastim
• Biosimilar G-CSF in Emerging Markets
• Five-year Sales of Leading Somatropin Brands (US$ M)
• Gentropin Sales, 2003-2012 (US$ M)
• Humatrope Sales, 2003-2012 (US$ M)
• Norditropin Sales, 2003-2012 (DKK & US$ M)
• Nutropin Sales, 2003-2012 (US$ M)
• Saizen Sales, 2003-2012 (EUR & US$ M)
• Biosimilar HGH in Emerging Markets
• Gonal-f US Patents
• Gonal-f Sales, 2003-2012 (EUR & US$ M)
• Biosimilar FSH in Emerging Markets
• Five-Year Sales of Leading Insulin Brands (US$ M)
• Humulin Sales, 2003-2012 (US$ M)
• Humalog US Patents
• Humalog Sales, 2003-2012 (US$ M)
• Lantus US Patents
• Lantus Sales, 2003-2012 (EUR & US$ M)
• Apidra US Patents
• Apidra Sales, 2008-2012 (EUR & US$ M)
• Levemir US Patents
• Levemir Sales, 2005-2012 (DKK & US$ M)
• NovoRapid & NovoMix US Patents
• NovoRapid & NovoMix Sales, 2005-2012 (DKK & US$ M)
• Five-year Sales of Leading Interferon Alfa Brands (US$ M)
• Five-year Sales of Leading Interferon Beta Brands (US$ M)
• PegIntron US Patents
• PegIntron Sales, 2003-2012 (US$ M)
• Pegasys US Patents
• Pegasys Sales, 2003-2012 (CHF & US$ M)
• Avonex US Patents
• Avonex Sales 2003-2012 (US$ M)
• Rebif Sales, 2003-2012 (EUR & US$ M)
• Betaferon/Betaseron & Extavia Sales, 2003-2012
(EUR & US$ M)
• Biosimilar Interferon in Emerging Markets
• Five-Year Sales of Enbrel and Leading Monoclonal
Antibodies (US$ M)
• Enbrel US Patents
• Enbrel Sales by Company, 2003-2012 (US$ M)
• Remicade US Patents
• Remicade Sales by Company, 2003-2012 (US$ M)
• Rituxan/MabThera Sales, 2003-2012 (CHF & US$ M)
• Herceptin US Patents
• Herceptin Sales, 2003-2012 (CHF & US$)
• Humira US Patents
• Humira Sales by Company, 2003-2012 (US$ M)
• Avastin Sales, 2004-2012 (CHF & US$ M)
• Erbitux Sales by Company, 2004-2012 (EUR & US$ M)

About the Author

The report has been researched and written by experienced independent market analyst, Karen Holmes. Karen has over 17 years pharmaceutical and healthcare market analysis experience.