A Decade of Biosimilar Filgrastim Experience Highlights the Scientific Basis for Extrapolation, Study Says

Sandoz’s biosimilar filgrastim was first approved in Europe in 2009 under the name Zarzio (later, the same drug was approved as Zarxio in the United States). Since that time, the number of biosimilars approved for use in the oncology field has grown substantially, and a recent review says that the past decade of experience with biosimilar filgrastim underscores the strong scientific basis for the extrapolation of indications for biosimilars.

As with most biosimilar products, filgrastim was studied in a phase 3 confirmatory clinical trial in the most sensitive population. In the case of EU registration for the filgrastim biosimilar, that population was patients with breast cancer undergoing myelosuppressive chemotherapy in the EP06-301 study. In the US context, data supporting approval were derived from PIONEER, also conducted among patients with breast cancer. Indications in stem cell mobilization and severe chronic neutropenia indications were approved on the basis of extrapolation, with the provision of a separate assessment, scientific rationale, and scientific justification.

Clinical experience with the biosimilar since the initial EU approval had provided additional evidence of the biosimilar’s efficacy and safety, and MONITOR-GCSF, a prospective, observational study among 1447 patients with cancer in 12 European countries, has underscored the fact that the biosimilar is effective and has a safety profile consistent with the known profile of filgrastim. Subanalyses of MONITOR-GCSF have also shown the efficacy and safety of the biosimilar in hematological and solid malignancies, including diffuse large B-cell lymphoma, non-small cell lung cancer, and breast cancer.

Additionally, a large body of evidence has accrued for the biosimilar’s use in autologous stem cell mobilization. In 27 studies conducted among 1019 patients, stem cell mobilization in the autologous setting showed that the efficacy and safety of the biosimilar is consistent with the known profile of the reference.

While most data for the biosimilar’s use in stem cell mobilization is in the autologous setting, evidence is also emerging in allogenic stem cell mobilization, and based on the comprehensive evidence available, the World Marrow Donor Association recently recommended using biosimilar filgrastim in healthy donors.

Additionally, among patients with chronic severe neutropenia, a registry study, for which final analysis is ongoing, has shown to date that patients who received biosimilar filgrastim between 2011 and 2018 have not reported serious adverse events.

“The experience from a decade of use of biosimilar filgrastim includes over 24 million patient-days of exposure and 10 years of real-world clinical evidence, indicating successful extrapolation,” write the review’s authors. This experience can help to reassure providers and patients that extrapolation is a scientifically justified practice, and that the process of biosimilar development and approval remains stringent.

Reference

Gascon P, Krendyukov A, Mathieson N, Mathieson N, Natek M, Aapro M. Extrapolation in practice: lessons from 10 years with biosimilar filgrastim [published online August 22, 2019]. BioDrugs. doi: 10.1007/s40259-019-00373-2.