On Thursday, July 13, 2017, FDA’s Oncological Drugs Advisory Committee (ODAC) unanimously recommended approval of biosimilars of two blockbuster cancer drugs. The first, Amgen and Allergan’s ABP-215, is a proposed biosimilar of Roche/Genentech’s Avastin (bevacizumab), a monoclonal antibody used in the treatment of a number of different cancers. The second, Mylan and Biocon’s MYL-1401O, is a proposed biosimilar of Roche/Genentech’s Herceptin (trastuzumab), a monoclonal antibody used in the treatment of HER2+ breast and gastric cancer. If, as expected, the drugs receive final FDA approval, each of these drugs will be the first U.S. biosimilar approved for its respective reference product.
Avastin, first approved in the United States in 2004, is a blockbuster cancer treatment that has been a popular target for biosimilar developers. Amgen now stands poised to be the first biosimilar maker with FDA approval for an Avastin biosimilar. Based on a comparative clinical study in patients with advanced non-squamous non-small cell lunch cancer and other evidence suggesting there were no clinically meaningful differences between ABP-215 and Avastin, ODAC recommended approval of ABP-215 for the following six indications:
Non-squamous non-small cell lung cancer (with carboplatin and paclitaxel for first line treatment of unresectable, locally advanced, recurrent or metastatic disease);
Metastatic colorectal cancer (with intravenous 5-fluorouracil–based chemotherapy for first- or second-line treatment);
Metastatic colorectal cancer (with fluoropyrimidine-irinotecan- or fluoropyrimidineoxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line Avastin-containing regimen);
Glioblastoma (as a single agent for adult patients with progressive disease following prior therapy);
Metastatic renal cell carcinoma (with interferon alfa); and
Cervical cancer (in combination with paclitaxel and cisplatin or paclitaxel and topotecan in persistent, recurrent, or metastatic disease).
The use of clinical data for one indication to support a finding of biosimilarity for other licensed-indications is known as extrapolation. Determining when extrapolation across indications may be appropriate is still a hot topic in the development of FDA regulatory guidance. However, ODAC’s willingness to extrapolate to five other indications for ABP-215 indicates that FDA may take a liberal view of extrapolation in the oncology sphere as it has in other areas to date. ODAC did not consider at this time whether to approve ABP-215 for Avastin’s other licensed indications because those indications are protected by orphan drug exclusivities expiring in 2021 and 2023.
Herceptin, first approved by FDA in 1998, is also a blockbuster product for Roche. Mylan is one of a number of biosimilar makers hoping to launch a Herceptin biosimilar but was the first to get a positive recommendation from the FDA staff and now the ODAC. Mylan and Roche/Genentech reached a confidential settlement and license agreement in March 2017, with Mylan withdrawing two inter partes review challenges to Genentech’s U.S. patents. The launch date for Mylan’s Herceptin biosimilar is not disclosed.
Mylan sought approval of its biosimilar for all three indications for which Herceptin is licensed: for the treatment of metastatic breast cancer, as adjuvant treatment for breast cancer, and for the treatment of metastatic gastric cancer. The advisory committee recommended approving Mylan’s biosimilar for all three indications. However, Herceptin’s indication for gastric cancer, is protected by orphan drug exclusivity expiring on October 20, 2017. Mylan therefore cannot obtain approval for the gastric cancer indication until after that.
Notably, Amgen and Mylan each also have pending applications for these biosimilars under evaluation by the European Medicines Agency (EMA). While the EU has typically taken the lead in the approval of biosimilar drugs, Mylan’s and Amgen’s U.S. applications are now on track to receive approval before their European counterparts. The EMA is also evaluating three other applications for proposed biosimilars of Herceptin and one other for Avastin.