Biosimilars Arrive at the FDA: Market Competition for Biologics Begins with Today's Preliminary FDA Staff Approval

This is a watershed week for biotech drugs (more formally known as biologics). Biotech drugs represent the culmination of molecular investigations into disease processes in order to identify when the use of a natural molecule (e.g., an antibody) offers a targeted treatment to specifically selected patients (e.g, Herceptin for breast cancer, Gleevec for leukemias). In 2014, the FDA issued 41 new drug approvals, a relatively high volume as compared to previous years. Biologics comprise a significant sector of drug approvals: these biotech drugs are often developed as targeted therapies and generally produced with biological processes, rather than chemical synthesis. Biologics have been available for several decades and often command significant (and sometimes unaffordable) prices; in general, there has been no "generic" market competition for a pioneer biologic in the U.S. (reproducing a biologic with high fidelity is more challenging than for standard chemically synthesized pharmaceuticals because the biologic is produced by biological processes). However, 2014 was the year in which the U.S. saw the opening moves in the efforts to bring biosimilars (or follow-on biologics) to the market. With the passage of the Affordable Care Act (ACA), the Biologics Price Competition and Innovation Act of 2009 (BPCIA), as part of that legislation, took effect in 2010. The BPCIA designed an abbreviated approval pathway for products shown to be biosimilar to or interchangeable with the original reference biologic product: 

Under the BPCI Act, a sponsor may seek approval of a “biosimilar” product under new section 351(k) of the PHS Act.  A biological product may be demonstrated to be “biosimilar” if data show that the product is “highly similar” to the reference product notwithstanding minor differences in clinically inactive components and there are no clinically meaningful differences between the biological product and the reference product in terms of safety, purity and potency. 

In order to meet the higher standard of interchangeability, a sponsor must demonstrate that the biosimilar product can be expected to produce the same clinical result as the reference product in any given patient and, for a biological product that is administered more than once, that the risk of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of maintaining the patient on the reference product. Interchangeable products may be substituted for the reference product by a pharmacist without the intervention of the prescribing health care provider.

The recent law is somewhat similar in concept (if not exact details) to the Hatch-Waxman Act of 1984, which designed a generic drug approval process for standard pharmaceuticals. The BPCIA contains the kind of tradeoffs that were seen in Hatch-Waxman, where the generic follower can rely on clinical data developed by the first manufacturer and thus avoid de novo clinical trials, while the first company is rewarded with one or more periods of market exclusivity. From the date of first licensure of the licensed biologic referenced in the biosimilar application, there is a 12-year market exclusivity period accorded to the first biologic. This period is independent of any patent rights that may pertain to the product. Several key developments related to the BPCIA occurred in 2014. In July of last year, the FDA received its first biologics license application (BLA) for a biosimilar version of Amgen's biologic Neupogen, filed by Novartis. The Oncologic Drugs Advisory Committee of the FDA will meet this week to take up the Novartis application. Today's release of a preliminary approval by the FDA staff of the proposed biosimilar ("there are no clinically meaningful differences in the effectiveness") is a watershed development that precedes the meeting this week. 

In another recent legal development, the BPCIA lays out a complicated set of patent-related information exchanges between the first biologic manufacturer and the biosimilar follower. In the recent opinion from the Federal Circuit, Sandoz v. Amgen, the court affirmed a district court’s refusal to entertain allegations of irregularities in the patent information scheme by the biosimilar entrant (Sandoz) against the pioneer manufacturer (Amgen). The Federal Circuit did not find declaratory judgment jurisdiction where Sandoz had not yet made a formal biosimilar application to the FDA, and would not consider its allegations out of turn from the sequence of events dictated by the BPCIA. With these recent moves from the FDA and the Federal Circuit,  the age of biosimilars in the U.S. - anticipated for some years - will begin to take concrete shape in 2015.