Further Guidance on Biosimilars Needed from FDA

The approval of the first biosimilar for market in the U.S. highlights the importance of further clarification from FDA on key policies related to the development and prescribing of highly similar biologics for patients. In announcing approval of Sandoz’ biosimilar to Amgen’s Neupogen (filgrastim), FDA’s Center for Drug Evaluation and Research (CDER) had to give Zarxio a “placeholder” nonproprietary name – filgrastim-sndz – pending agency decisions on the highly controversial issue of biosimilar “naming.” Brand firms insist that biosimilars are sufficiently different to warrant different names, while generics makers maintain that biosimilars should be able to use the same international nonproprietary name (INN) as the brand to ensure appropriate tracking and dispensing.

The approval of Zarxio as a biosimilar, but not an interchangeable therapy, also raises numerous questions from consumers and prescribers over possible differences in the Sandoz and Amgen products. Novartis’ Sandoz unit did not seek interchangeability, deciding it was enough of a challenge to test the new simplified pathway for biosimilars, pending further guidance from FDA on how to design and conduct “switching” studies to support automatic substitution by pharmacists. But FDA did approve Zarxio for all five Neupogen approved indications, supporting the strategy that biosimilar sponsors may extrapolate safety and efficacy data from one use to another based on analytical assays and biopharmaceutical testing that documents product comparability and lack of meaningful differences in patient response.

CDER’s guidance wish-list for this year includes advisories on demonstrating interchangeability to a reference product, on biosimilar labeling, and on statistical approaches to evaluating similarity data. Another document will aim to answer broader questions related to biosimilar development and approval. So far, FDA is setting clinical trial requirements for biosimilars on a case-by-case basis, but further clarification of standards for these products should encourage more biopharmaceutical companies to enter the field. Four other biosimilar applications have been filed with FDA, and several more are in the works, including some expected to seek interchangeable status.

Sandoz also will be paving the way for marketing and educational programs for biosimilars as it seeks to clarify for prescribers and patients the suitability of a product that is “highly similar” but different from a reference drug, and the meaning of data extrapolation and product interchangeability. FDA decisions on biosimilar naming may further shape policies set by CDER’s Office of Prescription Drug Promotion (OPDP) on whether biosimilar marketers may claim that a product “works the same” or is “just as safe” as the brand, and what data is needed to substantiate economic claims, such as “more affordable.” Instead of claiming clinical superiority, marketers may emphasize product quality, including the company’s record for safe manufacturing, product stability, and meaning of a “finger print” designation. OPDP also may have its eye out for messages from brands that disparage approved biosimilars as less safe and inferior.

However, Sandoz will delay marketing of Zarxio pending resolution of a legal battle over patent issues raised by Amgen. A federal judge in California is slated to consider Amgen’s injunction request this week in the first test of the complex “patent dance” provisions in the biosimilars legislation approved five years ago.

John Jenkins, director of CDER’s Office of New Drugs, acknowledged in a press call that one aim of biosimilar approval is to support greater competition in the biopharmaceutical market, which should enhance patient access to important therapies.  While CDER will continue to look to its advisory committees to evaluate most new biosimilars, particularly those involving new molecules or raising unique scientific issues, the need for this added review may diminish as FDA becomes more familiar with biosimilar development.