ESMO 2019 Features Data on Biosimilar Pegfilgrastim and Filgrastim

While much of the discussion about biosimilars in the oncology space has been circling around anticancer biosimilars, which have recently been making headway in the United States, supportive care biosimilars—including granulocyte colony-stimulating factor (G-CSF) agents—continue to occupy an important place in the oncology landscape. During this week’s European Society for Medical Oncology (ESMO) Congress 2019, held September 27 to October 1 in Barcelona, Spain, researchers presented data on biosimilar pegfilgrastim and filgrastim.

Sandoz’s biosimilar pegfilgrastim shows similar PK, PD, tolerability, and immunogenicity to reference

In late 2018, Sandoz’s pegfilgrastim biosimilar was approved in the European Union under the name Ziextenzo, and the drug maker is currently awaiting the FDA’s regulatory decision on the biosimilar.

In April 2019, Sandoz resubmitted its Biologics License Application for its biosimilar pegfilgrastim to the FDA after having received a 2016 Complete Response Letter for the product, and the resubmission included new data from a pivotal pharmacokinetic (PK) and pharmacodynamic (PD) study that compared the proposed biosimilar with the US-sourced and EU-sourced reference pegfilgrastim, Neulasta, and established a bridge between the 2 reference products.

During the ESMO meeting, researchers provided a detailed look at this 3-treatment, 6-sequence crossover study.¹

The study included 577 healthy volunteers who were given pegfilgrastim once per treatment period. The primary objectives included demonstrating PK similarity in terms of area under the curve from zero to the last measurable concentration (AUC_0-last) and PD similarity in absolute neutrophil count from the time of dosing to the last measurable concentration (AUEC_0-last). The study was powered to achieve confidence intervals within a prespecified biosimilarity margin of 0.8-1.25 in pairwise comparisons.

For the biosimilar versus the US reference, the ratio of AUC_0-last for the biosimilar to the US reference was 1.0635 (90% CI, 1.0087-1.1213), and the ratio of AUEC_0-last was 0.9997 (90% CI, 0.9912-1.0082). For the biosimilar versus the EU reference, the ratio of AUC_0-last was 1.0469 (90% CI, 0.9929-1.1038), and the ratio of AUEC_0-last was 1.0012 (90% CI, 0.9927, 1.0098). Finally, for the US reference versus the EU reference, the ratio of AUEC_0-last was 0.9844 (90% CI, 0.9336-1.0380), while the ratio of AUEC_0-last was 1.0015 (90% CI, 0.9930-1.0101).

In addition to demonstrating PK and PD similarity, safety was similar across groups, as was the incidence of antidrug antibodies.

For patients with rest periods in chemotherapy, low febrile neutropenia incidence with biosimilar filgrastim

International guidelines recommend using G-CSF agents to prevent febrile neutropenia in patients undergoing chemotherapy, and research has demonstrated that, while G-CSFs were once underused because of their expense, cost-saving biosimilar options have brought their use largely in line with guidelines set by the European Organisation for Research and Treatment of Cancer.

However, there remain questions about how best to treat patients who are being given chemotherapy regimens that involve a rest period of up to 14 days, either within one cycle or between different cycles of cytotoxic administration.

During ESMO 2019, attendees heard results of the multicenter TOPAZE study, conducted in France, which sought to describe the modalities of the clinical use of biosimilar filgrastim in patients whose regiments included rest periods.²

In total, 1080 patients were enrolled in the study, and 953 of them were included in the full analysis set. In total, 144 had lymphoma (of whom 39 had diffuse large B-cell lymphoma and 105 had Hodgkin lymphoma) and 809 had solid tumors (of whom 299 had breast cancer, 144 had lung cancer, and 366 had gastrointestinal cancers).

Those who had solid tumors were scheduled to receive filgrastim on day 2 of treatment for up to 5 days, whereas those with lymphoma were scheduled to receive filgrastim on day 3 for 4 to 8 days.

Among the patients who were receiving chemotherapy for curative intent, febrile neutropenia was reported in 2 patients with gastrointestinal cancer, 1 patient with lung cancer, and 7 patients with lymphoma, demonstrating that biosimilar filgrastim treatment in patients with rest periods had a low incidence of febrile neutropenia in the real-world setting, wrote the authors.

References

1. Velinova M, et al. Randomized, double-blind, cross-over phase I study comparing pharmacokinetics, pharmacodynamics, safety and immunogenicity of a biosimilar pegfilgrastim with EU and US references. Presented at: European Society for Medical Oncology Congress 2019; September 27 to October 1, 2019; Barcelona, Spain. Abstract 1815P.

2. Phelip JM, et al. Modalities of biosimilar filgrastim use in clinical practice in > 1000 patients receiving chemotherapy regimens with a rest period of ≤ 14 days: the TOPAZE study. Presented at: European Society for Medical Oncology Congress 2019; September 27 to October 1, 2019; Barcelona, Spain. Abstract 1812P.