The Food and Drug Administration has approved Zarxio (filgrastim-sndz), a biosimilar to filgrastim (Neupogen, marketed by Amgen Inc.). The drug binds to the granulocyte colony-stimulating factor (G-CSF) receptor, and is widely prescribed to treat neutropenia. The approval of Zarxio is the first biosimilar product approved in the United States.
Zarxio is approved for the same indications as Neupogen, which are:
* For patients with cancer receiving myelosuppressive chemotherapy;
* For patients with acute myeloid leukemia receiving induction or consolidation chemotherapy;
* For patients with cancer undergoing bone marrow transplantation;
* For patients undergoing autologous peripheral blood progenitor cell collection and therapy; and
* For patients with severe chronic neutropenia.
"Biosimilars will provide access to important therapies for patients who need them," then-FDA Commissioner Margaret A. Hamburg, MD, said in a news release. "Patients and the health care community can be confident that biosimilar products approved by the FDA meet the agency's rigorous safety, efficacy, and quality standards."
In a unanimous vote earlier this year, the Oncologic Drugs Advisory Committee to the FDA had recommended that the agency approve the biosimilar based on its safety and efficacy data, as well as evidence of the benefits of its use in more than 40 countries outside of the U.S. over the past 20 years (OT 2/10/15 issue).
A biosimilar product is a biological product-derived from a living organism including humans, animals, microorganisms, or yeast-that is approved based on showing that it is highly similar to an already-approved biological product, known as a reference product. The biosimilar must also show it has no clinically meaningful differences in terms of safety and efficacy from the reference product. Only minor differences in inactive components are allowable in biosimilar products.
A biosimilar product can be approved by the FDA only 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 Biologics Price Competition and Innovation Act of 2009 (passed as part of the Affordable Care Act in 2010) created an abbreviated licensure pathway for biological products shown to be biosimilar to or interchangeable with an FDA-licensed biological product, 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.
Evidence Review
The FDA's approval of Zarxio was 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 a news release from the FDA.
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.
In a news release from the manufacturer, Louis Weiner, MD, Director of Lombardi Comprehensive Cancer Center at Georgetown University, noted: "Filgrastim has proven clinical value in treating patients at increased risk of neutropenia, but it is underused in the U.S. for a variety of reasons, including price. Biosimilars have the potential to increase access-and the approval of Zarxio may reduce costs to the health care system. The comprehensive data set supports its use in clinical practice."
The most common expected side effects of Zarxio are aching in the bones or muscles and redness, swelling, or itching at injection site. Serious side effects may include spleen rupture; serious allergic reactions that may cause rash, shortness of breath, wheezing, and/or swelling around the mouth and eyes; fast pulse and sweating; and acute respiratory distress syndrome.
Nonproprietary Naming Policy
For this approval, the FDA designated a placeholder nonproprietary name of "filgrastim-sndz," noting, though, that the provision of such a placeholder name should not be viewed as reflective of the agency's decision on a comprehensive naming policy for biosimilar and other biological products. And while the agency has not yet issued draft guidance on how current and future biological products marketed in the U.S. should be named, the agency intends to do so in the near future, the FDA news release notes.