The US Food and Drug Administration (FDA) has approved the leukocyte growth factor Zarxio (filgrastim-sndz), the first biosimilar product to be approved in the US.
A biosimilar product is approved based on data showing that it is highly similar to an already-approved biological product.
Sandoz Inc’s Zarxio is biosimilar to Amgen Inc’s Neupogen (filgrastim), which was originally licensed in 1991. Zarxio is now approved for the same indications as Neupogen.
Zarxio can be prescribed for:
- patients with cancer receiving myelosuppressive chemotherapy
- patients with acute myeloid leukemia receiving induction or consolidation chemotherapy
- patients with cancer undergoing bone marrow transplant
- patients undergoing autologous peripheral blood progenitor cell collection and therapy
- patients with severe chronic neutropenia.
Zarxio is marketed as Zarzio outside the US. The biosimilar is available in more than 60 countries worldwide.
“Biosimilars will provide access to important therapies for patients who need them,” said FDA Commissioner Margaret A. Hamburg, MD.
“Patients and the healthcare community can be confident that biosimilar products approved by the FDA meet the agency’s rigorous safety, efficacy, and quality standards.”
Zarxio data
The FDA’s approval of Zarxio is based on a review of evidence that included structural and functional characterization, in vivo data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrates Zarxio is biosimilar to Neupogen.
The PIONEER study was the final piece of data the FDA used to approve Zarxio as biosimilar to Neupogen. The data was sufficient to allow extrapolation of the use of Zarxio to all indications of Neupogen.
In the PIONEER study, Zarxio and Neupogen both produced the expected reduction in the duration of severe neutropenia in cancer patients undergoing myelosuppressive chemotherapy—1.17 and 1.20 days, respectively.
The mean time to absolute neutrophil count recovery in cycle 1 was also similar—1.8 ± 0.97 days in the Zarxio arm and 1.7 ± 0.81 days in the Neupogen arm. No immunogenicity or antibodies against rhG-CSF were detected throughout the study.
The most common side effects of Zarxio are aching in the bones or muscles and redness, swelling, or itching at the 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.
About biosimilar approval
The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) was passed as part of the Affordable Care Act that President Barack 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, known as 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 it 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.
There must be no clinically meaningful differences between the biosimilar and the reference product in terms of safety and effectiveness. Only minor differences in clinically inactive components are allowable.
Zarxio has been approved as a biosimilar, not an interchangeable product. Under the BPCI Act, a biological product that has been approved as “interchangeable” may be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference product.
For Zarxio’s approval, the FDA has designated a placeholder nonproprietary name for this product as “filgrastim-sndz.” The provision of a placeholder nonproprietary name should not be viewed as reflective of the agency’s decision on a comprehensive naming policy for biosimilars and other biological products.
While the FDA has not yet issued draft guidance on how current and future biological products marketed in the US should be named, the agency intends to do so in the near future.
For more details on Zarxio, see the full prescribing information.
