On November 19, 2015, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) gave a positive opinion, recommending marketing authorization of Benepali, the first biosimilar of Enbrel (etanercept), in Europe.  Enbrel is a blockbuster treatment for rheumatoid arthritis and a number of other autoimmune conditions associated with elevated levels of tumor necrosis factor alpha (TNF-alpha), a protein that plays an important role in promoting inflammation.

Enbrel is marketed by Pfizer in Europe and by Amgen in the US.  It was first approved for sale in Europe in 2000 and in the US in 1998 for rheumatoid arthritis.  Enbrel was later approved for additional uses based on further clinical trials.  Benepali is expected to receive marketing approval by the European Commission in early 2016 based on its similarity to Enbrel and will be marketed by Samsung Bioepis, a joint venture between Samsung Biologics and Biogen.

Benepali, a complex biologic, will be in a category of its own when it comes to other biosimilars in Europe.  It is a soluble dimeric receptor fusion protein made by recombinant DNA technology in mammalian cells that blocks the activity of TNF-alpha by preferentially binding to it and preventing its binding to cellular receptors.  TNF-alpha is found at elevated concentrations in patients with the conditions treated by Enbrel: rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis and plaque psoriasis. The CHMP recommended approval of Benepali for all of these conditions.

In the US, FDA recently accepted Sandoz’s regulatory application for its proposed biosimilar of Enbrel for review.  Enbrel is a much more complex product than Sandoz’s Zarxio, a biosimilar of Amgen’s Neupogen and the only approved US biosimilar to date.  Sandoz is seeking approval for all of Enbrel’s indications.  FDA’s review of Sandoz’s proposed biosimilar will provide important information on the requirements for biosimilarity and extrapolation for more complex products.