The FDA’s Oncologic Drugs Advisory Committee (ODAC) recommended in an 11 to 0 vote (and 1 absentee) to approve carfilzomib (Kyprolis; Onyx), a new-generation proteasome inhibitor, for the treatment of patients with refractory and relapsed multiple myeloma who have failed at least 2 other myeloma therapies—the proteasome inhibitor bortezomib (Velcade) and the immunomodulatory drug lenalidomide (Revlimid).
The company applied for accelerated approval of this agent based on the results from a phase 2 clinical trial of 266 patients with refractory and relapsed myeloma who had received at least 2 previous treatments (with lenalidomide and with bortezomib), resulting in an approximate 22% overall response rate (ORR). However, the toxicity profile was problematic. The side effects seen in this study included serious heart problems, such as cardiac arrest, chest pain, pneumonia, and shortness of breath, including 5 deaths. According to the FDA report, >70% of patients receiving carfilzomib had lung complications.
The ODAC report says that because the ORR for carfilzomib was “only 22% in the primary efficacy study, it may not provide an advantage over available therapy. FDA is very concerned with the severe toxicities, including deaths, that are associated with the use of this agent. The pathogenesis of these toxicities is not understood.” However, the ODAC report states that carfilzomib’s benefits outweigh its risks, and is recommending its approval by the FDA. (June 20, 2012)
