乌鸦传媒

WASHINGTON -- The FDA has approved panobinostat (Farydak) as a third-line option for multiple myeloma.

Panobinostat is the first histone deacetylase (HDAC) inhibitor to receive a myeloma indication.

The stipulates use of panobinostat in patients who have received at least two prior treatments, including exposure to bortezomib (Velcade) and an immunomodulating agent. Additionally, the new indication calls for administration of the HDAC inhibitor with bortezomib and dexamethasone.

"Farydak 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," , of the FDA Center for Drug Evaluation and Research, said in a statement. "Farydak's approval is particularly important because it has been shown to slow the progression of multiple myeloma."

The FDA action followed a November 2014 advisory committee decision that the drug's benefits did not outweigh potential risks for patients with relapsed myeloma. The approval request initially sought an indication for relapsed/refractory myeloma in second line. Drug manufacturer Novartis subsequently submitted additional data to support a different indication: relapsed/refractory myeloma exposed to at least two prior therapies, including both bortezomib and an immunomodulator.

Supporting information for the approval application came from safety and efficacy data for 193 clinical trial participants who had relapsed or progressed following treatment with bortezomib and an immunomodulator. The patients were randomized to bortezomib and dexamethasone with or without panobinostat.

Patients randomized to the panobinostat arm had a median progression-free survival of 10.6 months as compared with 5.8 months for patients who received bortezomib and dexamethasone with placebo. The panobinostat arm had a 59% response rate versus 41% for the placebo group.

The most common side effects associated with panobinostat were diarrhea, fatigue, nausea, vomiting, fever, weakness, and peripheral edema. The most frequently reported laboratory abnormalities were hypophosphatemia, hypokalemia, hyponatremia, a rise in serum creatinine, thrombocytopenia, leukopenia, and anemia.

Panobinostat carries a boxed warning related to severe diarrhea and to severe and potentially fatal cardiac events, as well as cardiac arrhythmias and ECG changes.

FDA review of panobinostat for myeloma occurred through the agency's accelerated approval program, which allows approval of a drug that has demonstrated an effect on a surrogate endpoint that is likely to predict clinical benefit for patients who have a serious or life-threatening disease. In accordance with the accelerated approval process, the FDA granted panobinostat both priority review and orphan drug designation.