In only the second decision of its kind, the U.S. Food and Drug Administration (FDA) approved Celltrion’s biosimilar Inflectra™ (infliximab-dyyb), a reproduction of Janssen Biotech’s immunosuppressant Remicade® (infliximab). Inflectra is, however, the first biosimilar monoclonal antibody to be approved in the U.S.

The FDA’s Arthritis Advisory Committee had overwhelmingly recommended the approval of Inflectra by a vote of 21-3 in February. Inflectra has also previously been approved in Canada, Mexico, Australia, and several European markets.

Although now approved by the FDA, it is unclear when Pfizer, which has the marketing rights to Inflectra, will actually enter the U.S. market. Pfizer will likely wait for the conclusion of ongoing litigation between Celltrion and Janssen including whether Celltrion met the disclosure and advance-notice provisions of the Biologics Price Competition and Innovation Act (BPCIA).

The BPCIA is an analog of the ‘Hatch-Waxman Act’ which regulates generic small molecule drugs. To meet the ‘highly similar’ standard laid out in the BPCIA, a biosimilar product must have “no clinically meaningful difference” in terms of safety and effectiveness from the reference product. A generic small molecule drug on the other hand, need only show ‘substantial equivalence’ between the generic and reference drug which can be satisfied with analytic and purity data. Although the market for biosimilars is highly profitable (a single dose of Remicade can cost from $1,300 to $2,500), the price of developing a biosimilar is similarly as costly, upwards of $50m – a large difference from the $1-5m to develop a generic.

In a previous case, the Federal Circuit in Amgen Inc. v. Sandoz Inc. interpreted the BPCIA as provided two alternative routes for an abbreviated Biologics License Application (aBLA) filer to enter the market.1 An aBLA could 1) participate in the BPCIA’s so called “patent dance” by exchanging specific product and patent information regarding their aBLA to the reference product sponsor according to a prescribed timeline,2 or 2) provide the reference product sponsor with a 180-day notice including manufacturing information before commercial launch.3 The court ruled that a biosimilar applicant that opts out of the BPCIA’s so-called “patent dance” must wait 180 days after it provides a post-approval notice of commercial marketing to the reference product sponsor before it can market its biosimilar. The court also held that effective notice of commercial marketing can only be given after the FDA has licensed (approved) the product. Both Amgen and Sandoz havefiled a writ of certiorari with the Supreme Court.

The Federal Circuit in Amgen Inc. v. Sandoz Inc. had left open the question of whether the 180-day advance notice provision of the BPCIA is mandatory even when the biosimilar applicant participates in the patent dance – i.e. if the 180-day advance-notice mandatory in all circumstances. This is currently before a Massachusetts federal district court in Janssen Biotech Inc. v. Celltrion Healthcare Co. Ltd.4 Celltrion is arguing that because it did in fact participate in the patent dance, it is not required to provide a 180-day notice of commercial marketing. Janssen, on the other hand, is arguing that the 180-day notice is mandatory in all circumstances.

If the Massachusetts’ court finds the 180-day notice mandatory in all circumstances, it will in effect grant the branded biologics companies six months of exclusivity beyond the FDA’s approval. A finding that that the 180-day notice is not mandatory in all circumstances, on the other hand, thus allowing aBLA filers earlier entry into the market, may incentivize companies to participate in the patent dance regardless of the potentially cumbersome and unpredictable nature of the patent information exchange requirements.