The FDA has announced accelerated approval of carfilzomib (Kyprolis) as treatment for relapsed or refractory multiple myeloma (MM).
The drug is indicated for 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 treatment.
Carfilzomib was approved under the FDA’s accelerated approval program, which allows the agency to approve a drug based on data suggesting a clinical benefit. The drug’s maker is required to submit additional information after the approval to confirm that benefit.
Carfilzomib’s approval was based on efficacy data from a trial of 266 patients and safety data from 526 patients who received the drug.
The 266 patients had relapsed MM and had received at least 2 prior therapies, including bortezomib and an immunomodulatory agent (either thalidomide or lenalidomide). Patients received carfilzomib intravenously over a period of 2 to 10 minutes on 2 consecutive days a week for 3 weeks, followed by a 12-day rest period.
Patients received 20 mg/m2 at each dose in cycle 1 and 27 mg/m2 in subsequent cycles. They continued to receive treatment until their disease progressed, they developed unacceptable toxicity, or they completed 12 cycles.
Following treatment, the overall response rate was 22.9%. One patient achieved a complete response, 13 had very good partial responses, and 47 achieved partial responses. The median response duration was 7.8 months.
Researchers also evaluated carfilzomib’s safety in 526 patients with relapsed MM. Patients received a median of 4 treatment cycles and a median cumulative carfilzomib dose of 993.4 mg.
The most common adverse reactions—with an incidence of 30% or greater—were fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and pyrexia.
In addition, 45% of patients experienced serious adverse reactions. The most common were pneumonia, acute renal failure, pyrexia, and congestive heart failure.
Seven percent of patients (n=37) died on study. The most common causes of death, other than underlying disease, were cardiac (n=5), end-organ failure (n=4), and infection (n=4).
Carfilzomib will be marketed as Kyprolis by Onyx Pharmaceuticals. As a condition of the drug’s accelerated approval, Onyx is required to submit the complete analysis of an ongoing phase 3 trial comparing lenalidomide plus low-dose dexamethasone to lenalidomide, low-dose dexamethasone, and carfilzomib.
For more information on carfilzomib, consult the FDA website.
