The proteasome inhibitor carfilzomib (Kyprolis) did not meet its primary endpoint in the phase 3 FOCUS trial, according to the drug’s developers.
Single-agent carfilzomib did not improve overall survival compared to an active control regimen of corticosteroids plus optional cyclophosphamide in patients with relapsed and refractory multiple myeloma (MM).
This result raises questions about carfilzomib’s chances for regulatory approval around the world.
However, the companies developing the drug, Amgen and its subsidiary Onyx Pharmaceuticals, Inc., said results of the phase 3 ASPIRE trial should be sufficient to support carfilzomib’s approval.
At present, carfilzomib has accelerated approval from the US Food and Drug Administration for the treatment of MM patients who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of completing their last therapy.
That approval was based on response rates observed with carfilzomib. For the drug to gain full approval, it must demonstrate a clinical benefit.
The FOCUS trial
For the FOCUS trial, researchers enrolled 315 patients with relapsed and advanced refractory MM.
Patients were randomized to receive carfilzomib or an active control regimen consisting of low-dose dexamethasone, or equivalent corticosteroids, plus optional cyclophosphamide.
Nearly all patients in the control arm received cyclophosphamide. Patients were heavily pretreated and had received a median of 5 treatment regimens prior to study entry.
The trial’s primary endpoint was overall survival, and there was no significant difference between the 2 treatment arms. The hazard ratio was 0.975.
Treatment discontinuation due to adverse events and on-study deaths were comparable between the treatment arms. The rate of cardiac events in the carfilzomib arm was consistent with the current US label.
However, there was an increase in the incidence of renal adverse events of all grades observed in the carfilzomib arm compared to the active control arm and the label.
Full prescribing information for carfilzomib is available at www.kyprolis.com.
Amgen and Onyx said detailed results from the FOCUS trial will be submitted for presentation at an upcoming scientific meeting.
