Richard Pazdur, MD
The FDA approved carfilzomib (Kyprolis, Onyx) for patients with multiple 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 the completion of the last therapy.
While there was some concern over potentially lethal side effects during the time that the FDA reviewed the drug, the government agency decided that the benefits outweigh the risks.
Carfilzomib, a proteasome inhibitor delivered intravenously, was approved in large part due to the results of PX-171-003, a phase II trial that enrolled 266 patients with relapsed or refractory multiple myeloma who had received at least two prior lines of therapy. The study found that 61 of 266 patients (22.9%; 95% CI, 18%-28.5%) experienced complete or partial disappearance of their tumors with a median duration of response of 7.8 months (95% CI, 6.5-9.7).
“The approval of Kyprolis provides a treatment option to patients with multiple myeloma whose disease has progressed despite use of available therapies,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research, in a statement released on Friday. “We are encouraged by the continued progress in the development of drugs for multiple myeloma over the past decade, offering improved treatment of this disease.”
In its review of the drug, the FDA raised concerns over the risk of developing cardiac and pulmonary toxicities as well as hepatic impairment, which was responsible for two life-threatening cases of hepatic failure. In its approval, the FDA noted that side effects such as fatigue, low blood cell count and blood platelet levels, shortness of breath, diarrhea, and fever were observed in more than 30% of patients who received the drug in clinical trials, and that patients who develop heart failure and shortness of breath should be monitored closely. However, the options these patients have are limited.
“There is no current standard of care for these patients,” said Helen Torley, Chief Commercial Officer for Onyx Pharmaceuticals, noting that the drug could prove beneficial to as many as 10,000 to 15,000 patients who fit the criteria to receive the drug.
The decision was announced about a week prior to the action date of July 27, 2012. Last month, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 11-0 with one abstention in favor of recommending the drug. While the FDA is not required to follow the advice of the ODAC, the government agency usually does.
To date, this is the first and only approved indication for carfilzomib. There are currently three phase III trials under way that continue to test the effectiveness of the drug in multiple myeloma patients by measuring overall survival and comparing it with other anticancer agents and chemotherapy, including bortezomib.