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Multiple myeloma drug receives accelerated approval
The FDA granted accelerated approval to the injection drug carfilzomib for the treatment of patients with multiple myeloma who received at least two prior therapies, including bortezomib and an additional immunomodulatory agent.
Patients also must demonstrate disease progression on or within 60 days of the completion of the last therapy.
Carfilzomib (Kyprolis, Onyx Pharmaceuticals) is a proteasome inhibitor that disrupts the growth of cancer cells.
The FDA based its approval on the results of a phase 2, single-arm, multicenter trial in which researchers evaluated the efficacy of carfilzomib.
Researchers enrolled 266 patients with refractory multiple myeloma who received two prior lines of therapy, including bortezomib (Velcade, Millennium Pharmaceuticals) and thalidomide (Thalomid, Celgene) or lenalidomide (Revlimid, Celgene).
Investigators administered carfilzomib intravenously over 2 to 10 minutes on 2 consecutive days weekly for 3 weeks, followed by a 12-day rest period in a 28-day treatment cycle.
Patients received 20 mg/m² at each dose in cycle one and 27 mg/m² in ensuing cycles.
The overall response rate was 22.9% (95% CI, 18-25.5).
The most common adverse events observed in multiple clinical trials in patients with multiple myeloma were fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea and pyrexia.
Forty-five percent of patients reported serious adverse events, including pneumonia, acute renal failure, pyrexia and congestive heart failure.
Onyx will still submit a complete analysis of an ongoing randomized phase 3 trial comparing lenalidomide plus low-dose dexamethasone with lenalidomide plus low-dose dexamethasone plus carfilzomib as a condition of the accelerated approval.
In June, the FDA’s Oncologic Drugs Advisory Committee expressed its support for carfilzomib’s approval, voting 11-0 with one abstention.
Perspective
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Perspective
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I was hopeful and supportive of the drug approval based on the data. Bortezomib, a first-in-class proteasome inhibitor, made a dramatic difference in myeloma management. The addition of a new generation of proteasome inhibitors was the next natural step in treatment of this disease. Because of differences in specific aspects of the mechanism of action, carfilzomib shows different clinical activity and toxicity profiles, including very limited peripheral neuropathy. Importantly, it is able to overcome resistance in different patient subgroups, specifically in patients refractory to bortezomib and other novel myeloma treatments. Having another single-agent active in 20% to 30% of heavily pre-treated patients is a welcome change in myeloma management. I cannot be more grateful to the FDA for foreseeing the significance of this drug.