Jostling for position continues in biosimilars market

The jostling for position and future share of the increasingly attractive biosimilar market continues to gather momentum – yesterday came news that Merck & Co has licensed an Enbrel biosimilar and Actavis is seeking an emerging market partner to develop its own copycats of the world’s biggest biologics.

Merck’s targeting of Amgen’s Enbrel is logical given it was the biggest-selling biological product in the US in 2010 with sales of $3.3bn and loses patent protection next year. Although the patent cliff for biologics is not as dramatic as that afflicting small molecule drugs, biological products account for 20% of the total $130bn US sales at risk over the next six years. As for Actavis, EvaluatePharma data reveals it is unlikely to be short of partnering opportunities, with over 80 companies, mostly in emerging markets, already marketing or developing biosimilar products (see tables below).

Competition afoot

Merck licensed global rights to HD203 from Korean company Hanwha, for an undisclosed sum. Hanwha is currently conducting a therapeutic equivalence phase III trial of HD203 against Enbrel in Korea, although no clinical trials of the biosimilar have yet been conducted in the US or Europe.

Meanwhile, Claudio Albrecht, Actavis’ chief executive, told Bloomberg the European generics giant is looking at ways to develop its biosimilar capabilities, particularly against the big selling cancer antibodies, such as Avastin.

The table below reflects the height of the patent cliff currently facing the industry, with biological products set to make up an increasing proportion of the drugs at risk of generic competition. The data are slightly updated from an earlier patent cliff analysis by EP Vantage (Patent storm gathering strength, January 28, 2011).

Sales at risk ($bn; annual US sales in year prior to patent expiry)
Product patent expires in: All products Biological products % Biologicals at risk
 2009  15.0  0.0  0%
 2010  14.7  0.7  5%
 2011  16.1  0.3  2%
 2012  34.9  3.4  10%
 2013  20.3  7.5  37%
 2014  20.7  3.2  15%
 2015  25.8  7.4  29%
 2016  12.1  4.1  34%
Total 2011- 2016 129.9 25.9 20%

Enbrel alone accounts for 10% of US sales at risk in 2012, while 2013 sees four biological blockbusters – Epogen, Avonex, Humalog and Procrit – under potential biosimilar threat.

Of course there is still the significant matter of US and European regulators rubber-stamping a regulatory pathway for biosimilars – lobbying by both sides of the debate continues although there is a feeling that within the next 18 months the process should be almost complete.

Which would bring Enbrel into play, as it is set to lose patent protection in October 2012 and its 12-year exclusivity expired in November 2010. Indeed, if 12 years of data exclusivity stands for biologics, as under existing US law, it will not offer much additional protection to the biggest biologics today.

As the table below shows, six of the top ten biggest selling biologics in the US have already gone beyond 12 years since FDA approval.

Top 10 US biotechnology products in 2010 US annual sales ($bn)
Rank Product Company FDA Approval Date 12yr Exclusivity Expiry Patent Expiry 2010 2011 2012 2013 2014 2015 2016 CAGR (10-16)
 1  Enbrel  Amgen  02-Nov-98  02-Nov-10  23-Oct-12  3.30  3.37  3.31  3.25  3.13  2.96  2.78  (3%)
 2  Remicade  Johnson & Johnson  24-Aug-98  24-Aug-10  31-Dec-18  3.10  3.15  3.20  3.10  2.96  2.77  2.62  (3%)
 3  Avastin  Roche  26-Feb-04  26-Feb-16  26-Feb-18  3.07  2.88  3.00  3.13  3.26  3.36  3.45  2%
 4  Rituxan  Roche  26-Nov-97  26-Nov-09  31-Dec-18  2.91  3.19  3.37  3.49  3.58  3.59  3.57  3%
 5  Humira  Abbott Laboratories  31-Dec-02  31-Dec-14  31-Dec-16  2.87  3.26  3.49  3.56  3.55  3.55  3.54  4%
 6  Lantus  Sanofi  20-Apr-00  20-Apr-12  12-Feb-15  2.83  3.13  3.40  3.59  3.68  3.42  2.80  (0%)
 7  Neulasta  Amgen  31-Jan-02  31-Jan-14  20-Oct-15  2.65  2.71  2.74  2.73  2.73  2.62  2.38  (2%)
 8  Epogen  Amgen  01-Jun-89  01-Jun-01  20-Aug-13  2.52  2.22  2.02  1.88  1.70  1.42  1.18  (12%)
 9  Herceptin  Roche  25-Sep-98  25-Sep-10  31-Dec-19  1.53  1.76  2.13  2.18  2.17  2.16  2.15  6%
 10  Avonex  Biogen Idec  17-May-96  17-May-08  30-May-13  1.49  1.54  1.54  1.47  1.38  1.20  1.02  (6%)
 Other products  31.1  34.1  38.6  43.5  49.2  54.0  58.3
 Total US biotechnology product sales  57.4  61.3  66.8  71.9  77.3  81.0  83.8  4%

What is also striking about these sales forecasts is how analysts appear to be predicting only a minimal impact from biosimilar competition. For example Enbrel sales decline only gradually between 2012 and 2016. Most commentators currently expect biosimilars to grab around 30% of an original drug's market and, far less severe than for conventional drugs, due to fewer competitors and higher development and manufacturing costs. Yet the figures above throw up the possibility that the impact of these copycats could be even more benign.

As for potential partners or acquisition targets for Actavis, the table below highlights some of the biosimilar companies that would fit the bill.

Indeed, if Actavis wants to jump on the Enbrel biosimilar bandwagon, another Korean player, LG Life Sciences, or Chinese company, Simcere Pharmaceuticals, already have candidates in development.

Korea is becoming quite a hub for companies developing biosimilar capabilities – aside from Hanwha and LG, the likes of Celltrion, Dong-A and Green Cross could attract interest from the generics players and big pharma alike.

Selected companies with disclosed biosimilar products: marketed + pipeline
Company Disclosed biosimilar product types
Biocon MAb, insulin, EPO, CSF
BioGeneric Pharma EPO, CSF, growth hormone, interferon
Bioton Growth hormone
Cadila Pharmaceuticals MAb, interferon, EPO, CSF
Celltrion MAb
Dong-A Pharmaceutical EPO, CSF, interferon
Dr. Reddy's Laboratories MAb, EPO, CSF
Green Cross (Korea) MAb, factor VIII
Hanwha Group anti-TNF
Intas Pharmaceuticals CSF, interferon, EPO
ISU ABXIS MAb, enzyme replacement
JCR Pharmaceuticals EPO, FSH, enzyme replacement
Laboratorios Clausen Interferon
LG Life Sciences MAb, EPO, growth hormone
Nichi-Iko Pharmaceutical MAb
Schnell Biopharmaceuticals MAb, EPO
Simcere Pharmaceuticals anti-TNF
Tonghua Dongbao Insulin, CSF, interleukin
Wanbang BioPharma Insulin

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