FDA Warns of Increased Death Risk in Trial of New Myeloma Drug

The FDA issued a safety alert on the newly approved multiple myeloma drug melphalan flufenamide (Pepaxto), after a confirmatory trial evaluating the agent in the relapsed or refractory setting turned up an increased risk for death.

For those already receiving melphalan flufenamide, healthcare professionals are encouraged to review patients’ progress “and discuss the risks of continued administration with each patient in the context of other treatments,” the agency stated.

Wednesday’s warning stemmed from findings of the OCEAN trial, a phase III study comparing low-dose dexamethasone plus either melphalan flufenamide or pomalidomide (Pomalyst) in relapsed or refractory patients who have previously received two to four lines of therapy, plus those resistant to lenalidomide (Revlimid) as their last line of therapy.

“Due to the detrimental effect on overall survival in the OCEAN trial, FDA is requiring the manufacturer suspend enrollment in the trial,” the agency said.

Among the 495 patients in the efficacy analysis, deaths occurred in 48% of those in the melphalan flufenamide arm and 43% of those in the comparator arm. Median overall survival was 19.7 months and 25.0 months, respectively, with a hazard ratio for overall survival of 1.104 (95% CI 0.846-1.441), “indicating a detriment in survival in the melphalan flufenamide arm compared to the pomalidomide control arm,” according to an FDA analysis.

In February, the FDA granted accelerated approval to melphalan flufenamide, in combination with dexamethasone, for myeloma patients who have failed at least four prior regimens, and whose disease was refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody. Approval was based on results of the phase II HORIZON trial, but contingent upon confirmatory findings from OCEAN.

FDA on Wednesday said it may hold a future public meeting to discuss the new findings from OCEAN and “explore the continued marketing of Pepaxto.”

While enrollment in the study has been suspended, the FDA said patients who are receiving a clinical benefit from the drug can continue treatment in the trial provided they are informed of the risks and sign a revised written informed consent.

Drugmaker Oncopeptides AB will be required to suspend enrollment in other clinical trials involving melphalan flufenamide as well.

Last Updated July 28, 2021