The Food and Drug Administration has granted Priority Review designation to Kyprolis (carfilzomib) for the treatment of patients with relapsed multiple myeloma who have received at least one prior therapy.
Kyprolis is currently approved for the treatment of patients with myeloma who have received at least two prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of completion of the last therapy.
The Priority Review designation shortens the time to complete a drug's review and aims to deliver a decision on marketing approval designation for drugs that may offer major advances in treatment or provide a treatment where no adequate therapy exists within six months under the Prescription Drug User Fee Act (PDUFA). The FDA action date for Kyprolis for this indication is July 26.
The drug has been evaluated in combination with lenalidomide and low-dose dexamethasone versus lenalidomide and low-dose dexamethasone alone in 792 patients with relapsed multiple myeloma following treatment with one to three prior regimens in the international, randomized Phase III ASPIRE trial. Median progression-free survival for the patients receiving the three-drug combination (including Kyprolis) was 26.3 months compared with 17.6 months for those receiving the two-drug combination (without Kyprolis), according to the data presented at last year's American Society of Hematology Annual Meeting (OT 1/10/15 issue).
Safety data were evaluated in 526 patients with relapsed or refractory myeloma who received single-agent Kyprolis—there were 37 deaths in the Phase II studies (7% of the patients). The most common causes of death, other than disease progression, were cardiac events, end-organ failure, and infection.
Important warnings and precautions include cardiac arrest, congestive heart failure, myocardial ischemia, pulmonary hypertension, pulmonary complications, infusion reactions, tumor lysis syndrome, thrombocytopenia, hepatic toxicity, and embryo-fetal toxicity.
Death due to cardiac arrest occurred within a day of Kyprolis administration. Patients with New York Heart Association Class III and IV heart failure, myocardial infarction in the preceding six months and conduction abnormalities uncontrolled by medications were not eligible for the clinical trials. These patients may be at greater risk for cardiac complications, noted a news release from the drug's manufacturer, Onyx Pharmaceuticals, Inc.
The most common serious adverse reactions were pneumonia, acute renal failure, pyrexia, and congestive heart failure. The most common adverse reactions (an incidence of 30 percent or greater) observed in clinical trials of patients with multiple myeloma were fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and pyrexia. Serious adverse reactions were reported in 45 percent of patients.