The FDA has approved panobinostat (Farydak), in combination with bortezomib and dexamethasone, for treating patients with multiple myeloma.
Despite safety concerns, the US Food and Drug Administration (FDA) has approved the histone deacetylase (HDAC) inhibitor panobinostat (Farydak), in combination with bortezomib and dexamethasone, for treating patients with pretreated multiple myeloma. Panobinostat becomes the first HDAC inhibitor approved for the treatment of multiple myeloma.
“[Panobinostat] has a new mechanism of action that distinguishes it from prior drugs approved to treat multiple myeloma, making it a potentially attractive candidate agent for the treatment of multiple myeloma,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a press release. “[Panobinostat’s] approval is particularly important because it has been shown to slow the progression of multiple myeloma.”
The FDA’s Oncologic Drugs Advisory Committee concluded in November 2014 that panobinostat’s benefits did not outweigh its risks for relapsed multiple myeloma patients. Following that meeting, the drug’s manufacturer Novartis submitted data for this newly approved indication, patients who had previously received treatment with an immunomodulatory agent and bortezomib.
The randomized study that led to the approval was an international, placebo-controlled trial that included 193 patients with multiple myeloma who had received prior treatment with an immunomodulatory agent and bortezomib. Patients were treated with bortezomib and dexamethasone, plus either panobinostat or placebo. The median age among trial patients was 60 years (28–79).
The trial found that panobinostat improved median progression-free survival compared with patients receiving placebo (10.6 months vs 5.8 months; hazard ratio = 0.52; 95% CI, 0.36–0.76). Overall response rates were also improved in the panobinostat arm (58.5% vs 41.4%).
The most common adverse events (AEs; > 20%) among patients treated with panobinostat were decreased appetite, nausea, vomiting, swelling of the arms or legs, fever, diarrhea, tiredness, and weakness. The most common laboratory abnormalities were increased creatinine, thrombocytopenia, leukopenia, hyponatremia, hypophosphatemia, hypokalemia, and anemia. Serious AEs included diarrhea, pneumonia, thrombocytopenia, sepsis, and fatigue.
In the panobinostat arm of the trial there was an increased incidence in deaths not related to disease progression (7% vs 3.2%).
Panobinostat will carry a boxed warning due to the possibility of severe diarrhea and severe and fatal cardiac events. ECG changes were more frequent in the panobinostat arm of the trial (64% vs 42%), as were arrhythmias (12% vs 5%).
The drug is being approved with a Risk Evaluation and Mitigation Strategy (REMS) to inform of and help minimize these serious side effects.