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Biosimilars Law Blog
Posted in News & Events

The First Biosimilar in the U.S. – Five Questions Left Open by FDA

Last month, the Food and Drug Administration (FDA) approved the first U.S. biosimilar, Zarxio (filgrastim-sndz). Since the positive vote of FDA’s Oncologic’s Drugs Advisory Committee at its January meeting, approval of Sandoz’s biosimilar to Amgen’s Neupogen for all 5 Neupogen indications was anticipated. This landmark event comes almost exactly 5 years after passage of the Biologics Price Competition and Innovation Act and demonstrates that the pathway created by Congress can be used to get biosimilars to the U.S. market and to patients with FDA’s full confidence in the underlying science for the safety and efficacy of biosimilars.

However, the Zarxio approval leaves key FDA regulatory questions about the pathway unanswered.

  1. Although Zarxio was approved with the non-proprietary name, filgrastim-sndz, FDA was quick to point out this was a “placeholder” name and that the agency has not yet decided on its policy for naming of biologics and biosimilars, though it plans to issue guidance “in the near future.”
  1. Contrary to FDA’s own draft biosimilars guidance, there is no statement in the Zarxio labeling that identifies the product as a biosimilar , a biosimilar to Neupogen or not interchangeable with Neupogen. Further, Zarxio’s labeling follows a “generic drug” model; the labeling includes ONLY data derived from studies with Neupogen and NONE of the data generated with Zarxio in support of its approval. Because FDA has not yet issued detailed labeling guidance any policy reasons behind the Zarxio labeling have not been articulated.
  1. Extrapolation of indications. FDA had earlier suggested that extrapolation could be acceptable; the Zarxio approval provides the sense that the “scientific justification” for extrapolation requires a relatively low threshold when there is a common molecular mechanism of action even across different disease states. Sandoz provided clinical non-inferiority data to Neupogen in treatment of neutropenia in breast cancer patients receiving chemotherapy; Zarxio was approved for 4 indications related to neutropenia and one indication related to mobilization of cd34 cells. In the ODAC meeting materials, FDA discussed the common mechanism of action at the cellular level.
  1. Reference product. FDA appears flexible in its use of a non-U.S. reference product with the appropriate “scientific bridge” between the three products—biosimilar, U.S. reference product and non-U.S. reference product. The bulk of the non-clinical and clinical data were generated in comparison to the European version of Neupogen; only 2 of the 12 referenced studies compared Zarxio to the U.S.-approved Neupogen.
  1. Sandoz did not request an interchangeability designation for Zarxio, and so this first biosimilar does not provide any additional insight on expectations for interchangeability of biologics and biosimilars.

Interestingly, the Center for Medicare and Medicaid Services appeared to have been ready for the event, issuing three policy statements on reimbursement for biosimilars on the heels of the approval. Although not the final word on biosimilar reimbursement, these releases on Medicaid, Medicare Part B and Part D establish the initial CMS policies.