Biosimilars in Europe: 2016 Year in Review and What’s Ahead
Europe’s biosimilar market continues to develop, with biosimilars in new classes approved and pending in applications before the European Medicines Agency (EMA). 22 biosimilars are approved in eight different product classes and 16 biosimilar applications, including applications in four new product classes, are pending as of December 1, 2016. 2017 may see significant expansion of the biosimilars available in Europe.
Approved Biosimilar Products
The EMA approved four additional biosimilars in 2016, including three biosimilars in two new product classes: a biosimilar of Amgen’s Enbrel (etanercept) and two biosimilars of Sanofi’s Clexane (enoxaparin sodium). Etanercept is a fusion protein used to treat a variety of autoimmune disorders and enoxaparin sodium is a low-molecular weight heparin indicated for preventing blood clots. These additional approvals bring the total of currently authorized biosimilars in Europe to 22 and the product classes to eight as set forth below.
Biosimilar Products Approved by the EMA as of December 31, 2016 (1)
|Marketer||Active Substance||Reference Drug||Year of Approval|
|Epoetin Alfa Hexal||Hexal||epotein alfa||Eprex/Erypo||2007|
|Retacrit (2)||Hospira||epotein zeta||Eprex/Erypo||2007|
|Abasaglar (6)||Eli Lilly||insulin glargine||Lantus||2014|
|Low-Molecular Weight Heparins|
|Inhixa||Techdow Europe AB||enoxaparin sodium||Clexane||2016|
|Thorinane||Pharmathen S.A.||enoxaparin sodium||Clexane||2016|
|Flixabi (7)||Samsung Bioepis||infliximab||Remicade||2016|
|Benepali (9)||Samsung Bioepis||etanercept||Enbrel||2016|
(1) Three additional biosimilars were approved by the EMA but subsequently had their authorizations withdrawn.
(2) Biosimilar application to market in the United States was accepted for review by FDA but then rejected in its current form.
(3) Biosimilar application to market in the United States was accepted for review by FDA but has not been approved.
(4) Approved in the United States as a biosimilar under the Biosimilar Price Competition and Innovation Act of 2009 (BPCIA) with the trade name Zarxio.
(5) Approved in the United States under the 505(b)(2) pathway.
(6) Original EU trade name was Abasria; it was approved in the United States under the 505(b)(2) pathway with the trade name Basaglar and launched in the United States in December 2016.
(7) Biosimilar application to market in the United States is currently pending.
(8) Inflectra has been approved in the United States as a biosimilar under the BPCIA. Inflectra and Remsima are different trade names for the same monoclonal antibody.
(9) A different biosimilar of Amgen’s Enbrel, Sandoz’s Erelzi, has been approved in the United States as a biosimilar under the BPCIA.
Pending Biosimilar Applications
In addition to the 22 approved biosimilars, 16 additional biosimilar applications are under evaluation by the EMA as of December 1, 2016: four applications for biosimilars of AbbVie’s (adalimumab), two applications for biosimilars of Amgen’s Enbrel (etanercept), one application for a biosimilar of Sanofi’s Lantus (insulin glargine), one application for a biosimilar of Eli Lilly’s Humalog (insulin lispro), three applications for biosimilars of Amgen’s Neulasta (pegfilgrastim), two applications for biosimilars of Roche’s MabThera/Rituxan (rituximab) and three applications for Genentech’s Herceptin (trastuzumab). 12 of the pending applications seek to introduce biosimilars that fall into new product classes for the European market, i.e., biosimilars of adalimumab, pegfilgrastim, rituximab, and trastuzumab. EMA’s Committee for Medicinal Products for Human Use (CHMP) also recently issued a positive opinion for the first biosimilar, Celltrion’s Truxima, of Roche’s rituximab, a blockbuster monoclonal antibody for treating cancer. Truxima is expected to be approved in early 2017.
Richter withdrew its application for a biosimilar of Amgen’s Neulasta (pegfilgrastim), a long-acting version of Amgen’s Neupogen, in November 2016 after the CHMP indicated that the data did not support a positive benefit risk assessment. Other biosimilar makers have also encountered hurdles in obtaining approval for a Neulasta biosimilar. The FDA recently rejected Sandoz’s application for a biosimilar of Amgen’s Neulasta in its current form and Sandoz will be conducting further studies. (Sandoz’s application for a Neulasta biosimilar remains pending in Europe.) Similarly, Apotex’s application for a Neulasta biosimilar was submitted to FDA more than two years ago but has not been approved.
U.S. Forges Its Own Path
While Europe’s biosimilar pathway offers important lessons for the U.S., the FDA is setting its own path. Two of the four biosimilars approved in the U.S., Sandoz’s biosimilar of Amgen’s Enbrel and Amgen’s biosimilar of AbbVie’s Humira, were approved in the U.S. without any prior approval in Europe. Sandoz’s application for its biosimilar of Enbrel is pending before the EMA. It is one of two such applications. Amgen’s application for its biosimilar of Humira is also pending. It is one of four such applications before the EMA. Both products, a fusion protein and a monoclonal antibody respectively, are complex biologics.
In addition to approving products without any prior history in Europe, the FDA has also rejected applications for proposed biosimilars with authorization and marketing experience in Europe. Apotex’s proposed biosimilar of Amgen’s Neupogen (filgrastim) is one example. It was accepted by FDA for review in February 2015 but has not been approved. Approval in Europe, despite its significant experience with biosimilars, will not necessarily result in approval in the U.S.