FDA approval sought for once-weekly carfilzomib

Amgen have submitted a supplemental new drug application (sNDA) to the US Food and Drug Administration (FDA), for once-weekly dosing of carfilzomib (Kyprolis®) in combination with dexamethasone, in patients with relapsed and refractory multiple myeloma (RRMM).

The application was based on data from the phase III ARROW study, presented by Maria-Victoria Mateos at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting – read here and listen here. The study was conducted in collaboration with Philippe Moreau from the University Hospital of Nantes, Nantes, France, and was published in The Lancet Oncology on 1 June 2018.

In this trial, carfilzomib was administered at a dose of 70 mg/m² once-weekly (along with dexamethasone), instead of the usual twice-weekly dose of 27 mg/m². The study showed that patients receiving the once-weekly dosing had a median progression-free survival (PFS) of 11.2 months compared to 7.6 months for twice-weekly dosing. In addition, the overall response rate (ORR) in patients in the once-weekly arm was 62.9% (95% CI, 56.5-69.0), with 7% of patients also achieving a complete response or better, compared to an ORR of 40.8% (95% CI, 35.5-47.3) in the twice-weekly arm (P <.0001) and only 2% of patients in this arm achieving a CR. There was only a moderate increase in grade 3 (or greater) adverse events (68% vs 62%) for the once-weekly compared to twice-weekly, with complaints including anemia, pneumonia, diarrhea, and thrombocytopenia.

Given that this new regimen offers both improved efficacy and improved convenience for patients, there will be many people eagerly awaiting approval.