FDA's ODAC Recommends Approval of Biosimilar Bevacizumab and Trastuzumab

The FDA’s Oncologic Drugs Advisory Committee (ODAC) convened today to consider Biologics License Applications (BLAs) for 2 biosimilar products: ABP 215, Amgen’s bevacizumab biosimilar candidate (referenced on Avastin), and MYL-1401O, Mylan and Biocon’s biosimilar trastuzumab candidate (referenced on Herceptin).

During the consideration of ABP 215, FDA reviewers stated that they found no clinically meaningful differences between ABP 215 and the reference bevacizumab, adding to the totality of the evidence to support a demonstration of biosimilarity. The reviewers added that, in their view, an extrapolation of biosimilarity for all indications for which Amgen seeks approval is justified.

In a vote on whether the totality of the evidence supported licensure of ABP 215 as a biosimilar to Avastin for all of the indications sought by Amgen, all 17 committee members voted yes, based on what committee members called “clean and clear” evidence and “tight confidence intervals.”

However, during the discussion of their vote, some members of the committee raised lingering concerns: the group noted that pharmacovigilance for ABP 215 will be important moving forward. Some members of the committee also raised concerns about the homogeneity of the patient population studied in the clinical trials, noting that the patients were overwhelmingly white and exclusively male, and called for including a more diverse patients population.

In the second half of ODAC’s proceedings, the committee considered MYL-1401O. Presenting for the applicant, Hope Rugo, MD, clinical professor and director of the Breast Oncology Clinical Trials Program at the University of California at San Francisco, gave a clinical perspective in support of the drug. Rugo stated that trastuzumab is responsible for “curing women who otherwise would not be cured of breast cancer,” and that, if the biosimilar is approved, newly diagnosed patients with HER2-positive metastatic breast cancer will have the option to start their treatment with a lower-cost biosimilar. Other representatives for Mylan highlighted the fact that the patient population studied in its clinical trials was “a broad and sensitive treatment population.”

FDA reviewers, in summarizing their analysis of data provided by Mylan and Biocon, stated that the totality of the evidence supports demonstration of similarity, and no clinically meaningful differences were detected between the 2 products. Extrapolations to all indications sought by the biosimilar applicant is, the reviewers indicated, supported.

As the panel discussed the drug, the sponsor was called upon to address panelists’ questions concerning the following:

• Incidence of cardiac events in patients receiving trastuzumab
• Lot selection for the study
• Virtues of extrapolation for indications

As in the public comment portion of the proceedings on ABP 215, patient advocates broadly supported the approval of biosimilar trastuzumab to improve patient access. However, those speaking in support of MYL-1401O included such experts as Edward Li, PharmD, MPH, BCOP, professor of Pharmacy Practice for the University of New England College of Pharmacy, who urged the FDA to approve the biosimilar product in order to help control costs.

On the voting question of whether the totality of the evidence supported licensure of the product as a biosimilar product to Herceptin for all indications, all 16 attending committee members voted yes.

None of the committee members, either in the discussion of the drug or in the post-voting comments, raised questions or concerns related to Mylan and Biocon’s recent regulatory troubles abroad. On July 5, the French regulatory body, the National Agency for Medicines and Health Products Safety (ANSM) found that Biocon’s manufacturing facility in Bangalore had failed to follow good manufacturing practices for 3 biosimilar products, including MYL-1401O. The ANSM will re-inspect the facility, but the product’s European market entry could be delayed indefinitely until the European Medicines Agency is confident that the company has taken action to correct the deficiencies identified in the inspection.