FDA Approves First Biosimilar Drug to Enter U.S. Market

The FDA has approved its first biosimilar drug, opening up an era of market competition for biologic drugs (drugs produced in living cells rather than chemically synthesized). Sandoz (a division of Novartis) submitted an application for Zarxio, which is a biosimilar to Amgen’s drug Neupogen, used to stimulate the immune system and reduce the likelihood of infection, particularly for cancer patients undergoing chemotherapy. In January of this year, the FDA's Oncologic Drugs Advisory Committee (ODAC) recommended approval (see here), and the full agency has now issued its formal approval: 

The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) was passed as part of the Affordable Care Act that President Obama signed into law in March 2010. The BPCI Act created an abbreviated licensure pathway for biological products shown to be “biosimilar” to or “interchangeable” with an FDA-licensed biological product, called the “reference product.” This abbreviated licensure pathway under section 351(k) of the Public Health Service Act permits reliance on certain existing scientific knowledge about the safety and effectiveness of the reference product, and enables a biosimilar biological product to be licensed based on less than a full complement of product-specific preclinical and clinical data. 

A biosimilar product can only be approved by the FDA if it has the same mechanism(s) of action, route(s) of administration, dosage form(s) and strength(s) as the reference product, and only for the indication(s) and condition(s) of use that have been approved for the reference product. The facilities where biosimilars are manufactured must also meet the FDA’s standards. 

The FDA’s approval of Zarxio is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Zarxio is biosimilar to Neupogen. Zarxio has been approved as biosimilar, not as an interchangeable product. Under the BPCI Act, a biological product that that has been approved as an “interchangeable” may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product. 

The FDA has not approved Zarxio as an interchangeable product, so a prescribing physician will need to specify the biosimilar drug when prescribing. As the agency further develops its biosimilar approval processes, it will need to contend with the determination of interchangeability for a biosimilar to fully compete (or substitute) for the reference product. Nonetheless, the Zarxio approval shows that the FDA is now willing and able to evaluate biosimilar applications; more applications will follow. Now the field of biologic drugs begins to have its own long-awaited version of a “generic” approval pathway. Will price savings result? Biosimilars have been available in Europe for several years; results to date indicate that Zarxio has been priced around 25% less than the reference product. In general, the relatively high cost of biologic drugs and the resulting effect on access has created a strong demand for competition to emerge; this inaugural biosimilar approval is a start.