Sandoz Resubmits BLA for Pegfilgrastim Biosimilar

Sandoz announced today that it has resubmitted to the FDA its Biologics License Application (BLA) for its proposed biosimilar pegfilgrastim.

In July 2016, Sandoz revealed that it had received a Complete Response Letter for the proposed biosimilar, and stated at the time that it was working with the FDA to address the agency’s concerns. The newly resubmitted BLA includes new data from a pivotal pharmacokinetic (PK) and pharmacodynamic (PD) study.

The study was a single-dose, 3-period crossover study that compared the proposed biosimilar with the US-sourced and EU-sourced reference pegfilgrastim, Neulasta, and compared the US- and EU-sourced references.¹

In a statement announcing the resubmission, Mark Levick, MD, PhD, global head of development, biopharmaceuticals, Sandoz, said, “The US market is just beginning to benefit from biosimilars, as shown by the success of our filgrastim, the first approved biosimilar in the [United States]. The submission of our pegfilgrastim biosimilar application is another step for us as we continue to lead the way in creating early and expanded patient access to life-changing biologics.”

A previous study in healthy volunteers determined PK similarity, given that the 90% CI for the geometric mean ratio of the biosimilar versus the reference was within the prespecified similarity margin of 0.8-1.25. It also concluded that there was PD similarity between the products, given that the 95% CI for the ratio of the biosimilar versus the reference was within the same prespecified similarity margin.²

The new study was designed to address the high inter-subject variability (ISV) linked to target-mediated clearance with pegfilgrastim; the 3-way crossover design of the new study was intended to address ISV, as well as to provide a bridge between the EU and US reference pegfilgrastim products.

The molecule has also been studied in phase 3 clinical trials in patients undergoing chemotherapy.

Sandoz’s pegfilgrastim biosimilar is already approved in the European Union, where it received a marketing authorization in November 2018 under the name Ziextenzo.

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. Nakov R, Gattu S, Wang J, Velinova M, Skerjanec A. Proposed biosimilar pegfilgrastim LA-EP2006 shows similarity in pharmacokinetics and pharmacodynamics to reference pegfilgrastim in healthy subjects [abstract]. Cancer Res. 2018;78(4):nr P3-14-10. doi: 10.1158/1538-7445.SABCS17-P3-14-10.