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First Biosimilar Monoclonal Antibody in Oncology Granted EU Approval: Implications for the U.S. Market

March 14, 2017

First Biosimilar Monoclonal Antibody in Oncology Granted EU Approval: Implications for the U.S. Market

March 14, 2017

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Recent developments in Europe may augur a new push for oncology biosimilars in the United States. On February 22, 2017, the European Commission approved Celltrion’s TruximaTM for all indications of reference rituximab (marketed as Rituxan®), the world’s top selling cancer drug in 2015. TruximaTM, the first biosimilar monoclonal antibody approved in an oncology indication in Europe, is approved for the treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis.

Although there are currently no approved biosimilars in the United States with oncology indications, five other rituximab biosimilars, in addition to TruximaTM, are in development. Biosimilars for cancer immunotherapies, which mitigate the toxic side effects of chemotherapy, are especially promising because they are effective against many different types of cancer and offer the potential of long-term remission. At least two other follow-on oncology-based monoclonal antibodies are expected to reach the market along with rituximab in the near future: six biosimilars are in development for trastuzumab (marketed as Herceptin®), which targets certain breast cancers, and three biosimilars are in development for bevacizumab (marketed as Avastin®), which targets certain lung cancers. Both of these reference drugs face U.S. patent expiration in 2019.

Approval of the first oncology biosimilar in Europe bodes well for the potential approval in the U.S. because of the similarity of the approval processes for the European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA).  Both proceed in a stepwise approach, starting with structural and in vitro functional comparisons of the proposed biosimilar and the reference product followed by non-clinical in vivo animal studies and clinical studies. After these comparisons are completed, any residual uncertainty about biosimilarity is addressed through clinical testing, with at least one study assessing immunogenicity and pharmacokinetics or pharmacodynamics to demonstrate the safety, purity, and clinical efficacy of the biosimilar. Biosimilar approval is then granted based on the “totality” of evidence,” i.e., a comprehensive comparison of all the data.

Extrapolation of indications — approval of indications which have not been studied but for which the reference product is approved — is common in the United States and Europe. Because the clinical comparison between a biosimilar and its reference product is typically limited to one or two phase III comparative clinical trials, EMA and FDA guidance suggest that the most sensitive patient population and clinical endpoints should be used to detect differences in efficacy and safety between a biosimilar and a reference product. Extrapolation to other indications can then be justified based on biosimilarity and a similar mechanism of action in the different indications. For instance, the EMA approved TruximaTM for all indications based on clinical studies in patients with rheumatoid arthritis and advanced follicular lymphoma, a type of non-Hodgkin’s lymphoma, in part because of the similar mode of action across indications. Similarly, each of the four FDA-licensed biosimilars is approved across all indications of the reference product. The EMA and FDA both focus on confirming the similarity established by structural and functional characterization, and not re-establishing patient benefit.

A wave of oncology biosimilars is expected in the coming years as key U.S. patents expire. Biosimilar approvals in the U.S. and EU often lag one another depending on patent expiration dates. For instance, FDA approved the first U.S. biosimilar for Amgen’s Neupogen® (filgrastim) in 2015, two years after the patent expired in the United States. Neupogen® lost patent protection in the EU in 2007, and at least eight EU biosimilars for filgrastim were approved between 2008 and 2014. Given that the final EU patent for Rituxan® expired in 2013 and a key U.S. composition of matter patent allegedly expires in 2018, the U.S. may soon see a Rituxan® biosimilar. Indeed, although Celltrion has not yet announced an FDA application for a rituximab biosimilar, it has said one would be submitted sometime in 2017. Other oncology biosimilars may soon follow.


The world’s most sold cancer drugs in 2015, (Mar. 31, 2016),

Weise et al., Biosimilars: the science of extrapolation, Blood 124 No. 22.

U.S. Food and Drug Administration, Scientific considerations in demonstrating biosimilarity to a reference product (Apr. 2015).

European Medicines Agency, Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance. non-clinical and clinical issues (June 2013).

U.S. Food and Drug Administration, Guidance for Industry: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product (Apr. 2015).

European Medicines Agency, Guideline on similar biological medicinal products containing monoclonal antibodies – non-clinical and clinical issues (Dec. 2012).

Business Wire, Truxima, the first biosimilar mAb in oncology, granted EU marketing authorization, (Feb. 22, 2017),

Zachary Brennan, Waiting on the US: Rapid biosimilar uptake worldwide stalling, BioPharma-Reporter (Oct. 1, 2014),

Curiglianoa et. al, Biosimilars: Extrapolation for oncology, Critical Reviews in Oncology/Hematology, 104 (2016).

Gareth MacDonald, Celltrion’s MabThera cleared by EC for autoimmune diseases and cancer, (Feb. 22, 2017),

Authors: Tasha Francis, Ph.D., Jenny Shmuel, Ph.D.,  Ron Vogel

The opinions expressed are those of the authors on the date noted above and do not necessarily reflect the views of Fish & Richardson P.C., any other of its lawyers, its clients, or any of its or their respective affiliates. This post is for general information purposes only and is not intended to be and should not be taken as legal advice. No attorney-client relationship is formed.

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Jenny Shmuel, Ph.D. | Principal

Jenny Shmuel, Ph.D., represents clients on a range of intellectual property matters, with an emphasis on medical device and pharmaceutical technologies. She has extensive experience in pre-suit diligence, case management, expert and fact discovery, and brief writing, and has examined and cross-examined witnesses at trial. Over the last several...