First Biosimilar Approved in US: Filgrastim-sndz (Zarxio)

Zosia Chustecka


March 06, 2015

The first biosimilar product in the United States has been approved by the US Food and Drug Administration, in a move described by the agency's director, Janet Woodcock, as a "significant milestone." The product approved is the recombinant colony-stimulating factor filgrastim-sndz (Zarxio, Sandoz/Novartis), which has several clinical uses, including aiding recovery from neutropenia in cancer patients undergoing chemotherapy.

The agency noted that filgrastim-sndz is a placeholder nonproprietary name for this product.

Zarxio is already marketed in Europe and several other countries worldwide.

This new product is like a "generic" version of the brand-name filgrastim, marketed as Neupogen (Amgen), which was originally approved in 1991, and has enjoyed huge sales, topping more than $1 billion in 2014. However, generic is the term used when the drug is a chemical compound, whereas for recombinant biological products, the term "biosimilar" is used instead.

The agency followed the advice of its Oncologic Drugs Approval Committee, which voted unanimously to recommend approval at its recent January meeting after it concluded that the biosimilar was not clinically different from Neupogen. That FDA decision was described as "historic" by the Generic Pharmaceutical Association, adding that it "is an important step forward for cancer patients and all who are awaiting access to more affordable versions of lifesaving biologic medicines here in the United States."

Now the approval of the first biosimilar in the United States will be seen as a landmark, and will likely open the floodgates for many other biosimilar products in the near future.

Indeed, the agency's director predicts just that in a letter to FDA staff congratulating them on this "historic achievement."

"The approval of Zarxio is quite significant as it paves the way for the future of biosimilar approvals," she wrote. "A successful biosimilars review process will spark the development of a new segment of the biotechnology industry in the United States. It will also provide significant benefits for patients, making available more affordable treatments that clinicians will be assured are safe, effective, and of high-quality."

No Clinically Meaningful Differences

The FDA said that the approval of a biosimilar is based on data that show it to be 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.

The agency noted that its 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 demonstrate that Zarxio is biosimilar to Neupogen.

Zarxio is now approved for the same indications as Neupogen, which 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 FDA noted that the most common expected adverse effects of Zarxio are aching in the bones or muscles and redness, swelling, or itching at injection site. Serious adverse 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, which can lead to shortness of breath, difficulty breathing, or increase the rate of breathing.

Zarxio has been approved as a biosimilar, not as an interchangeable product, the agency notes. It adds that under the Biologics Price Competition and Innovation Act of 2009, a biological product 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. This does not apply to Zarxio, as it is not approved as an interchangeable.

In the case of Zarxio, the prescribing physician has to specify that the patient should receive Zarxio. This product can be used in patients who have previously been treated with Neupogen, commented John Jenkins, MD, director of the Office of New Drugs, Center for Drug Evaluation and Research, at the FDA. Speaking at an FDA press briefing, he said that physicians also have another choice of product, as there is also tbo-filgrastim (Sicor Biotech/Teva Pharmaceuticals), which was approved by the FDA in 2012.

Neupogen "is underused in the United States for a variety of reasons, including price," Louis Weiner, MD, chair of the Department of Oncology and director of the Lombardi Comprehensive Cancer Center at Georgetown University in Washington, DC, said in a statement issued by Novartis. "Biosimilars have the potential to increase access, and the approval of Zarxio may reduce costs to the healthcare system."

This is the big hope for biosimilars, that with them, "we will hopefully see lower prices," commented Dr Jenkins during the briefing.

At present, there is no word from Novartis on how it will price the new biosimilar, but the expectation is that it will be less expensive than Neupogen.

Express Scripts Holding Co., the largest pharmacy benefit manager in the United States, estimates that Neupogen costs about $3500 per year, according to a Bloomberg report. In the same report, Express estimates that if Zarxio is 30% cheaper than Neupogen, it could save the American healthcare system $5.7 billion in the next 10 years.


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