FROM AN FDA TELECONFERENCE
A biosimilar version of filgrastim, the leukocyte growth factor marketed as Neupogen, has been approved by the Food and Drug Administration, marking the first approval of a biosimilar product in the United States.
The filgrastim biosimilar will be marketed as Zarxio by Sandoz and is approved for the same indications as Amgen’s Neupogen , which was licensed by the FDA in 1991. There are at least four other biosimilar versions of biologic products currently being reviewed by the FDA, including an infliximab (Remicade) biosimilar. Biosimilars are expected to make biological therapies available at a lower price, improving access to these treatments, according to the FDA.
The approval of Zarxio is based on a 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,” according to the FDA’s March 6 statement announcing approval. A biosimilar must also have the same mechanism of action, route of administration, dosage form, and strength as the “reference” product, can only be approved for the same indications, and must be manufactured in facilities that meet FDA standards.
The approval is a result of the Biologics Price Competition and Innovation Act of 2009 ( BPCI ), which was passed as part of the Affordable Care Act, creating “an abbreviated licensure pathway for biological products shown to be ‘biosimilar’ or ‘interchangeable’ with an FDA-licensed biological product,” according to the FDA.
This pathway “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.”
“The intent of the BPCI act is to provide patients with access to lower-cost safe and effective biological products,” Dr. John K. Jenkins, director of the office of new drugs in the FDA’s Center for Drug Evaluation and Research (CDER), said during an FDA telebriefing on March 6.
“Patients and the health care community can be confident that biosimilars products approved by the FDA meet the agency’s rigorous safety, efficacy and quality standards and can be expected to be as safe and effective as the reference biological product,” he added.
Zarxio has not been approved as an “interchangeable” product. Under the BPCI Act, a biologic product that has been approved as interchangeable “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.” Dr. Jenkins said that “it is up to the prescriber” to indicate Zarxio or Neupogen when prescribing the product for a patient.
Sandoz does not yet know when Zarxio will be commercially available and is not providing information on the price of the product, but “is committed to bringing high-quality, competitively priced biosimilars to the U.S. market,” including Zarxio, according to a statement provided by a company spokesperson.
The approved indications for Zarxio and Neupogen are for treatment of patients with cancer receiving myelosuppressive chemotherapy; patients with acute myeloid leukemia receiving induction or consolidation chemotherapy; patients with cancer undergoing bone marrow transplantation; patients undergoing autologous peripheral blood progenitor cell collection and therapy; and patients with severe chronic neutropenia.
The nonproprietary name for Zarxio is “filgrastim-sndz.”
At a meeting in January, the FDA’s Oncologic Drugs Advisory Committee unanimously supported approval of Zarxio for the indications approved for Neupogen in the United States. With little debate, they agreed that, other than minor differences in clinically inactive components, Zarxio was “highly similar” to the reference product, and that there were “no clinically meaningful differences” between the two.
“Filgrastim has proven clinical value in treating patients at increased risk of neutropenia, but it is underused in the United States for a variety of reasons, including price,” Dr. Louis Weiner , chairman of the department of oncology and director of the Lombardi Comprehensive Cancer Center at Georgetown University, Washington, said in a statement issued by Sandoz announcing the approval. He spoke on behalf of Sandoz at the FDA advisory panel meeting.
The filgrastim biosimilar was approved in 2009 in the European Union, where it is marketed as Zarzio, and is approved in more than 60 countries, with more than 7.5 million days of exposure, according to Sandoz, a Novartis company.