Post-hoc analysis of the phase III ENDEAVOR trial shows Kyprolis (carfilzomib) reduces risk of death in multiple myeloma, and data submitted to FDA.-Amgen.

Amgen announced positive results from a post-hoc analysis requested by the FDA of the Phase III head-to-head ENDEAVOR trial, which followed patients with multiple myeloma for at least three years after enrollment. The analysis evaluated overall survival (OS) and long-term safety of Kyprolis (carfilzomib) administered at 56 mg/m2 twice weekly and dexamethasone (Kd) versus Velcade (bortezomib) and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma. Kd reduced the risk of death by 24 percent over Vd (median OS 47.8 months for Kd versus 38.8 months for Vd, HR=0.76, 95 percent CI, 0.63-0.92; p=0.0017). This Kd regimen is currently approved in the U.S., European Union and other countries based on the primary analysis of progression-free survival in the ENDEAVOR study.

In addition, Amgen announced that the FDA has accepted for review a supplemental New Drug Application based on the overall survival data from the Phase III head-to-head ENDEAVOR trial demonstrating that Kyprolis (carfilzomib) and dexamethasone (Kd) reduced the risk of death by 21 percent and increased OS by 7.6 months versus Velcade (bortezomib) and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma (median OS 47.6 months for Kd versus 40.0 months for Vd, HR=0.79; p=0.01). Adverse events observed in this updated analysis were consistent with those previously reported for ENDEAVOR. The most common adverse events (greater than or equal to 20 percent) in the Kyprolis arm were anemia, diarrhea, pyrexia, dyspnea, fatigue, hypertension, cough, insomnia, upper respiratory tract infection, peripheral edema, nausea, bronchitis, asthenia, back pain, thrombocytopenia and headache. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of April 30, 2018. If approved by the FDA, the Kyprolis U.S. prescribing information will include this data from the ENDEAVOR trial showing that Kyprolis, administered at the 56 mg/m2 dose as a 30-minute infusion twice weekly with dexamethasone, helped relapsed or refractory multiple myeloma patients live longer than patients administered Vd.