As Biosimilar Competition Nears for Pegfilgrastim, a Novel Long-Acting G-CSF Agent Shows Promise

While no biosimilar developer has gained regulatory approval for a pegfilgrastim biosimilar in the United States or the European Union, numerous companies are targeting the drug, and some hope to gain approvals and even launch products later this year. However, even as competition from biosimilars approaches, a novel granulocyte-colony stimulating factor (G-CSF) drug could also compete with the reference pegfilgrastim, Neulasta.

Eflapegrastim is novel long-acting granulocyte-colony stimulating factor therapy. Pharmacokinetic analysis in vivo demonstrated a 2- to 3-fold increase in area under the time‐concentration curve for absolute neutrophil count versus pegfilgrastim when administered at similar doses, and the proposed drug demonstrated comparable efficacy compared with pegfilgrastim in an open-label study in patients with breast cancer who were receiving docetaxel and cyclophosphamide.

The study, published last week in Cancer Medicine, was designed to evaluate the efficacy and safety of the eflapegrastim at 3 dose levels, and its primary efficacy endpoint was the duration of severe neutropenia during the first cycle of chemotherapy. In total, 148 patients were enrolled between 2013 and 2014 in 27 sites in 6 countries, and 147 patients were evaluable. Patients were given eflapegrastim at a dose of 45 μg/kg (n = 39), 135 μg/kg (n = 36), or 270 μg/kg (n = 36), or pegfilgrastim (n = 36).

Overall, 138 patients (93%) completed all 4 cycles of chemotherapy, and the following were observed across the 4 groups:

• Among patients who received the highest dose of eflapegrastim, 1 patient (3%) had severe neutropenia lasting 1 day.
• Among patients who received the lowest dose of eflapegrastim, 14 patients (36%) had severe neutropenia lasting 1 to 5 days.

• Among patients who received the medium dose of eflapegrastim, 7 patients (19%) had severe neutropenia lasting 1 to 7 days.
• Among patients who received pegfilgrastim, 5 (14%) had severe neutropenia lasting 1 to 3 days.

The rate of hospitalizations across all cycles was similar across treatment groups, with the highest incidence observed in the pegfilgrastim group (14%) and the lowest incidence observed in the group receiving the highest dose of eflapegrastim (3%).

Across all groups, 89% of patients experienced adverse events (AEs). The most commonly reported AEs, most of which were mild to moderate, were fatigue, alopecia, nausea, diarrhea, and bone pain. No neutralizing antibodies against eflapegrastim were detected in this study.

The authors concluded that eflapegrastim had comparable efficacy to pegfilgrastim on the duration of severe neutropenia, and that the proposed drug presented no new safety concerns.

Spectrum Pharmaceuticals, which is developing eflapegrastim, plans to submit a Biologics License Application to the FDA later this year.

Reference

Vacira JL, Chan A, Mezei K, et al. An open‐label, dose‐ranging study of Rolontis, a novel long‐acting myeloid growth factor, in breast cancer. Cancer Med-US. Published online March 23, 2018. https://doi.org/10.1002/cam4.1388.