Pepaxto Side Effects May Increase Risk of Death, FDA Warns Just Months After Approval

Federal drug regulators are warning about the side effects of Pepaxto, indicating the recently approved multiple myeloma drug may increase the risk of death.

In a Peptaxo drug safety alert issued on July 28, the FDA is alerting patients and healthcare professionals about data from a clinical trial study, which has linked the treatment to a higher than expected mortality rate. The warning comes just months after the drug hit the market.

Pepaxto (melphalan flufenamide) was given accelerated approval by the FDA in February 2021, for use with low-dose dexamethasone to treat patients with relapsed or refractory multiple myeloma after prior therapies failed. At the time, the agency required the manufacturer, Oncopeptides AB, to conduct a post-marketing clinical trial known as OCEAN.

According to the FDA’s warning, the ongoing trial is revealing a “detrimental effect on overall survival,” which has resulted in the FDA requiring the manufacturer to suspend enrollment in the study and all other ongoing Pepaxto clinical trials.

In a statistical analysis of the OCEAN findings (PDF), the FDA indicates 117 out of 246 participants, or 48%, died. That compares to 43% deaths among those given the multiple myeloma drug pomalidomide, which was being used as a control in the clinical trial.

The preliminary results also found the median overall survival of Peptaxo patients was 19.7 months, compared to 25 months among those using pomalidomide.

Drugs given accelerated approval are meant to be emergency drugs needed to fill a niche not filled by another drug, which could save patient lives. However, these findings indicate Pepaxto may actually be 10% more likely to lead to a patient death when compared to a drug already on the market, raising questions about use of the accelerated approval process.

In the meantime, the FDA says patients who are receiving a clinical benefit from the drug may continue to take it, but only if they are informed of the risks and sign a revised written informed consent.

“FDA continues to evaluate the OCEAN trial results and may hold a future public meeting to discuss these safety findings and explore the continued marketing of Pepaxto,” the FDA safety alert states. “The agency will update patients and health care professionals when new information is available.”

The agency is encouraging patients and healthcare professionals to report adverse health events linked to Pepaxto use to the FDA MedWatch Adverse Event Reporting Program.