FDA Advisors Unanimously Approve Sandoz Biosimilar

The main surprise at the Jan. 7, 2015 meeting of FDA’s Oncologic Drugs Advisory Committee (ODAC), which held a special session to assess the scientific data supporting FDA approval of its first biosimilar therapy, was the panel’s strong support for a drug developed under a very different model from most cancer therapies. The Sandoz unit of Novartis looks to make history in seeking licensure for its Zarzio as biosimilar to Amgen’s Neupogen (filgrastim). FDA reviewers had already issued detailed analyses of the sponsor’s analytical, preclinical and clinical studies and determined that the new product is “highly similar” and has “no clinically meaningful differences” to the reference product. FDA experts concluded that the application thus merits approval, and all 14 panel members agreed.

The committee further determined that the biosimilar should be licensed for all five approved indications of Neupogen. That clearly supports the concept of extrapolation of data for one indication to other approved uses based on documented similarity between the new drug and the reference product.

Novartis avoided controversy by not seeking interchangeability status for Zarzio (the U.S. name for Sandoz’ Zarxio marketed in Europe), although it’s already conducting further clinical trials to gain that status as the next step. There was little discussion of labeling and product naming, or of post-approval study requirements. Those hot-button issues were raised by public commenters, who weighed in on the value of less costly biosimilars to patients and the health care system and the pro’s and con’s of distinct vs. common product names. FDA lists biosimilar interchangeability and labeling on its guidance agenda for 2015, as well as further advice on statistical approaches and biosimilar program implementation.

Will doctors respond?

The focus of the health care community now shifts to how quickly clinicians adopt a biosimilar therapy, observes Tanisha Carino, executive vice president of Avalere Health. The positive ODAC vote, she notes, “provides a strong foundation” for physicians to consider the product as a safe alternative, but it remains to be seen if patient access and affordability issues drive prescribing.

Even if FDA approves Zarzio in time to meet a March 8, 2015 user fee goal, it may take some time for the new product to come to market. Amgen already went to court to block approval based on Sandoz’ failure to meet certain patent information exchange requirements of the Biologics Price Competition and Innovation Act. The court put the challenge aside pending product approval, but Amgen is expected to continue its opposition to the new competitor, and to push for distinct names for each biotech product -- even though it is developing several biosimilars itself.

Sandoz’ development program for Zarzio was complicated somewhat by relying on EU-licensed Neupogen as the reference product for most of its pre-clinical and clinical studies. But the sponsor conducted additional PK and PD bridging studies that produced sufficiently similar results for U.S. licensed Neupogen, the European reference product, and the new biosimilar. At the end of the day, Steve Koslowski, director of the Office of Biotechnology Products in the Center for Drug Evaluation and Research (CDER), calmed any lingering qualms among the advisors by emphasizing the need to consider the “totality of evidence” from analytics that support similarity – and opposed to examining the detailed data from each study.

In opening the ODAC meeting, CDER director Janet Woodcock noted that the pharmaceutical development community is extremely busy developing biosimilars, and that she expects this to be “the first of a number of meetings” on these products. There has been speculation about whether FDA will bring all biosimilar applications to advisory panels, and that now looks likely. That could affect the two other biosimilar applications announced by manufacturers. Canada-based Apotex recently filed an application for a biosimilar version of Amgen’s Neulasta, the long-acting formulation of Neupogen. And last August, Celltrion of South Korea said it was seeking FDA approval of a biosimilar version of Janssen’s Remicade.

The ODAC meeting was “an historic occasion,” said Woodcock, in that it marked the beginning of an FDA program that will provide benefits to the public. The last word came from ODAC patient representative  Randy Hillard; in announcing his vote in favor of approval, he added:  “I’m willing to bet my life on it.”