FDA Approves Sandoz's Pegfilgrastim Biosimilar, Ziextenzo

The FDA has approved Ziextenzo (pegfilgrastim-bmez), Sandoz’s biosimilar pegfilgrastim referencing Neulasta. The biosimilar was approved to decrease the incidence of infection, as manifested by febrile neutropenia, in patients receiving myelosuppressive anticancer treatment. Sandoz plans to launch the product this year.

“When a cancer patient with febrile neutropenia gets an infection, it can have serious consequences such as delays or dose reductions of chemotherapy,” said Carol Lynch, president of Sandoz Inc, in a statement announcing the regulatory decision. “The approval of Ziextenzo expands our oncology portfolio, providing physicians with a long-acting supportive oncology biosimilar option.”

The approval comes at the end of a long regulatory road for Sandoz; in 2016, Sandoz received a Complete Response Letter for the biosimilar, and in order to address the agency’s concerns, the biosimilar developer provided new data from a pivotal pharmacokinetic (PK) and pharmacodynamic (PD) study.

The study was a single-dose, 3-period crossover study that compared the biosimilar with the US-sourced and EU-sourced reference pegfilgrastim, and it compared the US and EU references.¹ The study sought to address the high inter-subject variability (ISV) linked to target-mediated clearance with pegfilgrastim; the 3-way crossover design was intended to address ISV and to provide a bridge between the EU and US reference pegfilgrastim products.

A previous PK study was conducted in healthy volunteers, and the biosimilar has also been studied in phase 3 clinical trials (PROTECT-1 and PROTECT-2) in patients undergoing chemotherapy.²

In a combined analysis of the safety of the biosimilar across those trials, researchers reported that there were no differences in adverse events (AEs) reported by patients receiving the biosimilar or the reference pegfilgrastim in the phase 3 studies. Differences in AEs reported by those enrolled in the phase 1 versus the phase 3 studies, they concluded, were likely related to differences in baseline health status, sex differences, and other patient factors.

The biosimilar is also approved in the European Union, where it received a marketing authorization from the European Commission in November 2018.

Ziextenzo joins 2 other approved biosimilar pegfilgrastim products in the United States: Mylan and Biocon’s Fulphila, and Coherus BioSciences’ Udenyca, both of which have launched in the US market. The approval also makes Sandoz the first biosimilar maker to have both a short-acting granulocyte colony-stimulating factor biosimilar (Zarxio) and a long-acting biosimilar option approved.

References

1. R Nakov, S Schussler, S Schier-Mumzhiu, et al. A large multi-center, randomized, double-blind, crossover study in healthy volunteers to compare pharmacokinetics and pharmacodynamics of a proposed biosimilar pegfilgrastim with EU and US reference pegfilgrastim: methodological approach. Ann Oncol. 2018;29(8)mdy300.110. doi: 10.1093/annonc/mdy300.110.

2. Harbeck N, Wang J, Otto GP, Gattu S, Krendyukov A. Safety analysis of proposed pegfilgrastim biosimilar in phase I and phase III studies [published online March 5, 2019]. Future Oncol. doi: 10.2217/fon-2018-0878.