The study randomized and dosed 589 patients with breast cancer with either the biosimilar, the EU-licenced reference pegfilgrastim, or the US-licensed reference pegfilgrastim.
Multiple drug makers are undertaking development of biosimilar pegfilgrastim, a long-acting granulocyte-colony stimulating factor therapy that can reduce the incidence of febrile neutropenia (FN). Among those drug makers is Apotex, which has developed a biosimilar that is approved in Canada under the name Lapelga (in the United States, Apotex was long embroiled in a legal case with Amgen, maker of the reference pegfilgrastim, Neulasta).
While a timeline for US regulatory consideration and potential approval of the biosimilar is not clear, a recently published paper reports on findings from a 3-way, randomized equivalence study for the biosimilar versus both US- and EU-licensed reference pegfilgrastim.
The study randomized and dosed 589 patients with breast cancer—at 56 center in 11 countries—who were scheduled to receive docetaxel, doxorubicin, and cyclophosphamide chemotherapy. A total of 294 patients received the biosimilar, 148 received the US reference, and 147 received the EU reference. The study’s primary endpoint, chosen for its sensitivity, was the assessment of the duration of severe neutropenia—defined as an absolute neutrophil count below 0.5 × 109/L—in the first cycle of chemotherapy.
For the as randomized population, the 95% confidence interval (CI) of the difference in mean duration of severe neutropenia in cycle 1 between the biosimilar and US reference was outside of the equivalence margin (±0.5 days) by 0.01 days, but the authors write that this difference is not considered clinically significant, and that an equivalence margin of  ±1 day is typical in such studies. The 95% CI of the difference in mean duration of severe neutropenia between the biosimilar and the EU reference, however, was contained within the pre-defined margin.
The number of adverse events (AEs) in the 3 treatment arms was similar. In total, 295 AEs were reported in the biosimilar group (89.7%), 128 were reported in the US reference group (94.8%), and 116 were reported in the EU reference group (92.8%). Most AEs were mild to moderate in severity, and the most commonly reported AEs were neutropenia and nausea. No unexpected safety events were reported in the biosimilar group, and no clinically meaningful effects associated with anti-drug antibodies were observed.
The authors concluded that these results demonstrate the similarity of the Apotex pegfilgrastim product to both the US- and EU-licensed reference in terms of both clinical efficacy and safety.
Desai K, Misra P, Kher S, Shah N. Clinical confirmation to demonstrate similarity for a biosimilar pegfilgrastim: a 3-way randomized equivalence study for a proposed biosimilar pegfilgrastim versus US-licensed and EU-approved reference products in breast cancer patients receiving myelosuppressive chemotherapy. Exp Hematol Oncol. 2018;7:22. doi: 10.1186/s40164-018-0114-9.