Inching Closer to the First Biosimilar Approval in the U.S.

Last week we saw some significant biosimilar activity in the U.S. Specifically, on January 7, 2015, a U.S. Food and Drug Administration (FDA) Advisory Committee (Advisory Committee) voted 14-0 to approve Sandoz Inc.’s (Sandoz) filgrastim biosimilar (referred to as “EP2006”) for all five indications of Neupogen® (the reference product manufactured by Amgen Inc. (Amgen)).  Specifically, the Advisory Committee found EP2006 to be “highly similar” to filgrastim, “notwithstanding minor differences in clinically inactive components,” and that “there are no clinically meaningful differences between EP2006 and filgrastim in terms of [purity], safety, and effectiveness.”  Typically, the FDA follows an Advisory Committee’s recommendation, although it is not required to do so.  Assuming the FDA follows the Advisory Committee’s recommendation, EP2006 would be the first biosimilar approved under the FDA’s 351(k) biosimilar pathway.  Sandoz manufactures a biosimilar version of filgrastim under the brand name Zarzio® in more than 40 countries. For example, Zarzio® was first approved in the European Union in 2009.

As mentioned above, EP2006 received a recommendation for approval in five indications (all of which are somewhat related):  (1) cancer patients receiving myelosuppressive chemotherapy; (2) patients with acute myeloid leukemia receiving induction or consolidation chemotherapy; (3) cancer patients receiving bone marrow transplant; (4) patients undergoing peripheral blood progenitor cell collection and therapy; and (5) patients with severe chronic neutropenia.  Interestingly, because Sandoz provided Phase III data for only one of the five indications, the remaining four indications were awarded by extrapolation.

Extrapolation is highly controversial but viewed as crucial in keeping the research and development costs down for biosimilars.  It will be interesting to see how the FDA handles extrapolation with more complex molecules (such as antibodies), which have been approved for very distinct applications (such as, for example, infliximab and adalimumab, which are approved for such distinct indications such as rheumatoid arthritis, ulcerative colitis and Crohn’s disease).  For example, in Europe, Celltrion Inc. (Celltrion) was able to fully extrapolate to six indications (including psoriasis and digestive disorders) for its biosimilar version of infliximab.  However,  extrapolation was not permitted in Canada where regulators found that differences between Celltrion’s biosimilar and the reference product raised questions about whether the biosimilar infliximab would be suitable for every condition.

Sandoz’ requested approval for EP2006 as a biosimilar to Neupogen® and not as an interchangeable product.  However, switching studies are in process that could support a future interchangeability application.  Publication of the FDA’s guidance document on interchangeability is expected in 2015.

One significant issue not discussed by the Advisory Committee or in its briefing document released prior the meeting was naming.  Will Sandoz’ product have the generic name filgrastim or some variant?  Novartis proposed the brand name, Zarxio for EP2006.  However, this brand name has not yet been approved by the FDA.  Industry is still waiting publication of the FDA’s guidance document on naming.

Despite the good news, significant challenges still remain for Sandoz and its biosimilar product.  On January 6, 2015, the day before the Advisory Board’s vote, Amgen filed a motion for partial summary judgment in its lawsuit filed against Sandoz on October 24, 2014.  Specifically, Amgen urged a California federal judge to find that pursuant to the Biologics Price Competition and Innovation Act (BPCIA) Sandoz was required to provide Amgen with a copy of its 351(k) application for its biosimilar product as well as its manufacturing information no later than 20 days after the FDA notified Sandoz of acceptance of its 351(k) application.  Additionally, Amgen requested that the judge find that Sandoz could not have provided notice of commercial marketing as required under the BPCIA because the FDA had not yet approved Sandoz’ 351(k) application.  Thus, according to Amgen, Sandoz’s conduct violated the BPCIA and this violation represented unfair competition under California law.  Unfortunately, this litigation will likely need to be resolved before EP2006 can enter the marketplace.  Resolution could be years away thus  further delaying entry of the first biosimilar product into the U.S. marketplace.

This post was written by Lisa Mueller.

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