Sandoz Biosimilar Approval Answers Questions On Labeling But Not Naming
Executive Summary
FDA approves Zarxio with a ‘placeholder’ name (filgrastim-sndz) that combines Neupogen’s nonproprietary name with a company-specific suffix, pending development of a naming guidance.
FDA approval of Sandoz Inc.’s Zarxio (filgrastim-sndz) – a biosimilar to Amgen Inc.’s Neupogen (filgrastim) – with a “placeholder” nonproprietary name suggests the agency is still working on its nomenclature policy for biosimilar products.
However, the first approval action under the abbreviated 351(k) pathway does provide a clear picture of the agency’s thinking on biosimilar product labeling. In short, the labels of biosimilars should look almost identical to those of their reference products.
FDA approved Zarxio on March 6 for all five indications on the label of Neupogen, a granulocyte colony-stimulating factor first approved in 1991 (see box).
Zarxio’s Indications
- Decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever
- Reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia
- Reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g.‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation
- Mobilize autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis
- Reduce the incidence and duration of sequelae of severe neutropenia (e.g.‚fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia
The ability to extrapolate across indications was one of the key reasons why the Novartis AG division opted to go down the 351(k) route rather than file a conventional BLA (Also see "Sandoz’s Filgrastim Biosimilar Relies On Data Extrapolation" - Pink Sheet, 24 Jul, 2014.).
Approval was widely expected by the application’s March 8 user fee date given the FDA review staff’s findings, presented at a Jan. 7 advisory committee meeting, that the Sandoz product was “highly similar” to Neupogen with no clinically meaningful differences (Also see "Sandoz’s Biosimilar Filgrastim ‘Highly Similar’ To Neupogen, FDA Staff Say" - Pink Sheet, 5 Jan, 2015.).
The Oncologic Drugs Advisory Committee voted unanimously in support of approval for all five indications (Also see "Sandoz’s Biosimilar Filgrastim Sails Through FDA Panel" - Pink Sheet, 7 Jan, 2015.).
Zarxio’s nonproprietary name combines that of the reference product – filgrastim – with the suffix “sndz,” reflecting the name of sponsor Sandoz.
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However, FDA was quick to point out that the nonproprietary name is merely a “placeholder” that is “not reflective of the agency’s decision on a comprehensive naming policy” for biosimilars (see related story, (Also see "Zarxio’s Placeholder Name Hints FDA Wants Generic Feel To Biosimilar Market" - Pink Sheet, 9 Mar, 2015.).
Label Mirrors Brand
While FDA’s position on nomenclature is still murky pending the development of a draft guidance, the Zarxio approval brings clarity to the agency’s views on biosimilar labeling.
With some small exceptions, the Zarxio label mirrors that of the reference product. All of the clinical safety and efficacy data in the biosimilar’s label are drawn from the studies conducted with Amgen’s product and reflected in the Neupogen label.
None of the data from the clinical studies Sandoz conducted are included in the biosimilar’s label (see related story, (Also see "Biosimilar Labeling Dissected: Sandoz’s Zarxio Uses Amgen’s Neupogen Text" - Pink Sheet, 9 Mar, 2015.).
In addition, the word “biosimilar” is not mentioned anywhere in Zarxio labeling.
“The FDA approval of Zarxio marks a significant milestone for the U.S. health care system and for patients who might suffer from neutropenia,” said Carol Lynch, global head of Biopharmaceuticals & Oncology Injectables at Sandoz.
“As the global leader in biosimilars, we are honored to be the first company to successfully work with FDA to navigate the U.S. biosimilar pathway and we look forward to making this high-quality biosimilar available to patients in the U.S.”
Post-Marketing Agreements
FDA's approval letter states that filgrastim-sndz drug substance will be manufactured at a Sandoz facility in Kundl, Austria. The final formulated drug product will be manufactured, filled, labeled and packaged at GP Grenzach Produktions GmbH in Grenzach-Wyhlen, Germany.
The approval carries a post-marketing requirement under the Pediatric Research Equity Act to “develop a presentation that can be used to directly and accurately administer filgrastim-sndz to pediatric patients who weigh less than 36 kg requiring doses that are less than 0.3 mL (180 mcg), and conduct any necessary human factors studies to evaluate the ability of caregivers to measure the appropriate doses.”
Zarxio labeling recommends against direct administration of less than 0.3 mL due to the potential for dosing errors with the prefilled syringe.
The approval letter also reflects six post-marketing commitments related to chemistry, manufacturing and controls.