FDA approves first biosimiar Zarxio

March 6, 2015

FDA approved filgrastim-sndz (Zarxio, Sandoz), the first biosimilar product approved in the United States.

FDA approved filgrastim-sndz (Zarxio, Sandoz), the first biosimilar product approved in the United States.

Biological products are generally derived from a living organism. They can come from many sources, including humans, animals, microorganisms or yeast.

A biosimilar product is a biological product that is approved based on a showing that it is highly similar to an already-approved biological product, known as a reference product. The biosimilar also must show it has no clinically meaningful differences in terms of safety and effectiveness from the reference product. Only minor differences in clinically inactive components are allowable in biosimilar products.

Zarxio is biosimilar to Amgen Inc.’s Neupogen (filgrastim), which was originally licensed in 1991. Zarxio is approved for the same indications as Neupogen, and can be prescribed by a healthcare professional for:

  • 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 approval of Zarxio, the first biosimilar product, offers alternative treatment option to the pre-existing indications for Neupogen, but ultimately this approval will allow more patients to have access to this agent,” said FormularyWatch advisor Abimbola Farinde, PharmD, MS, who serves on the faculty at Columbia Southern University, Orange Beach, Ala.

Related:Cancer biosimilar drug deemed similar to Neupogen

The approval was based on a comprehensive package of analytical, nonclinical, and clinical data, which confirmed that Zarxio is highly similar to the US-licensed reference product. The approval of Zarxio follows the unanimous positive vote in January by the Oncologic Drugs Advisory Committee (ODAC).

“Filgrastim has proven clinical value in treating patients at increased risk of neutropenia, but it is underused in the US for a variety of reasons, including price” Louis Weiner, MD, chairman of the department of oncology and director of the Lombardi Comprehensive Cancer Center at Georgetown University, said in a press release. “Biosimilars have the potential to increase access and the approval of Zarxio may reduce costs to the healthcare system. The comprehensive data set supports its use in clinical practice.”

NEXT: The head-to-head PIONEER study helped to approve Zarxio as biosimilar to the reference product

 

The pivotal head-to-head PIONEER study was the final piece of data contributing to the totality of evidence used by FDA to approve Zarxio as biosimilar to the reference product. Importantly, the data demonstrating high similarity was sufficient to allow extrapolation of use of Zarxio to all indications of the reference product. In the PIONEER study, Zarxio and the reference product both produced the expected reduction in the duration of severe neutropenia in cancer patients undergoing myelosuppressive chemotherapy (1.17 and 1.20 days for Zarxio and the reference product, respectively). The mean time to absolute neutrophil count recovery in cycle 1 was also similar (1.8 days ± 0.97 in Zarxio arm vs 1.7 days ± 0.81 in reference product arm). No immunogenicity or antibodies against rhG-CSF were detected throughout the study.

Related:Adoption of fast-growing biosimilars segment essential

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 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 FDA’s standards.

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 healthcare provider who prescribed the reference product.

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, a lung disease that can cause shortness of breath, difficulty breathing or increase the rate of breathing.

For this approval, the FDA has designated a placeholder nonproprietary name for this product as “filgrastim-sndz.” The provision of a placeholder nonproprietary name for this product should not be viewed as reflective of the agency’s decision on a comprehensive naming policy for biosimilar and other biological products. While the FDA has not yet issued draft guidance on how current and future biological products marketed in the United States should be named, the agency intends to do so in the near future.

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