FDA Approves First Biosimilar Product ZARXIO® – A Primer on Biosimilars

SUMMARY: The U.S. FDA on March 6, 2015 approved ZARXIO® (Filgrastim-sndz), the first biosimilar product approved in the United States. A biosimilar product is a biological product that is approved based on its high similarity to an already approved biological product (also known as reference product). Biological products are made from living organisms including humans, animals and microorganisms such as bacteria or yeast and are manufactured through biotechnology, derived from natural sources or produced synthetically. Biological products have larger molecules with a complex structure than conventional drugs (also known as small molecule drugs). Unlike biological products, conventional drugs are made of pure chemical substances and their structures can be identified. A generic drug is a copy of brand name drug and has the same active ingredient and is the same as brand name drug in dosage form, safety and strength, route of administration, quality, performance characteristics and intended use. Therefore, brand name and the generic drugs are bioequivalent.

The Affordable Care Act in 2010 created an abbreviated licensure pathway for biological products that are demonstrated to be “biosimilar” to, or “interchangeable” with an FDA-licensed (FDA approved) biological product (reference product). The biosimilar must show that it has no clinically meaningful differences in terms of safety and effectiveness from the reference product. A biosimilar product can only be approved by the FDA if it has the same mechanism of action, route of administration, dosage form and strength as the reference product, and only for the indications and conditions of use that have been approved for the reference product. Biosimilars are not as easy to manufacture as generics (copies of brand name drugs) because of the complexity of the structure of the biologic product and the process used to make a biologic product. The facilities where biosimilars are manufactured must also meet the FDA’s standards.

The FDA’s approval of ZARXIO® was 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 demonstrated ZARXIO® was biosimilar to NEUPOGEN®. ZARXIO® was approved as a biosimilar and not as an interchangeable product (Can only be substituted for the reference product after approval by the prescribing Health Care Provider). ZARXIO® is approved for the same indications as NEUPOGEN® and these indications include

• 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

• Patients with severe Chronic Neutropenia.

The most common expected side effects of ZARXIO® are bone and muscle aches, redness, swelling or itching at injection site. Less common, serious side effects include spleen rupture and serious allergic reactions. Unlike ZARXIO® which was approved via an abbreviated licensure pathway for biosimilars, GRANIX® (tbo-Filgrastim) was approved via the full Biologic License Application pathway, which presently limits GRANIX® use only for reducing the duration of severe neutropenia in patients non-myeloid malignancies, receiving myelosuppressive chemotherapy. The present Medicare reimbursement rules will be more favorable to ZARXIO® compared to GRANIX®, based on their approval process. FDA approves first biosimilar product ZARXIO®. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm436648.htm