FDA warns of increased death risk for new myeloma drug, raising prospect of potential market withdrawal

FDA Building
In warning the public of increased risk of death for Oncopeptides’ Pepaxto, the FDA said it will "explore the continued marketing" of the multiple myeloma drug. (FDA)

It was only February when the FDA granted an accelerated approval for Oncopeptides’ Pepaxto to treat relapsed or refractory multiple myeloma. But now the agency is alerting patients and doctors of the drug’s increased risk of death and opening the possibility of a potential market withdrawal.

Wednesday, the FDA issued a public alert, warning that Pepaxto, or melphalan flufenamide, may cause myeloma patients to die early, according to results from a confirmatory trial that’s required by the agency.

The FDA has suspended patient enrollment in all Pepaxto clinical trials. The agency may hold a public meeting to discuss the new safety signal and “explore the continued marketing of Pepaxto,” it said.

“Patient safety is paramount to Oncopeptides,” the Swedish firm said in a statement Wednesday. “The company has an ongoing dialogue with the FDA and will provide updated information as soon as more information becomes available.” 

The Stockholm-based company flagged the safety signal from the phase 3 OCEAN study earlier this month. It found that more patients treated with Pepaxto and the steroid dexamethasone died, compared with those who received Bristol Myers Squibb’s Pomalyst and dexamethasone. The risk of death was 10% higher for Pepaxto.

At the time, Oncopeptides said the surprising difference is “primarily explained” by pre-specified subgroups. The company plans to share detailed results of the trial at the International Myeloma Workshop meeting in September.

RELATED: Large differences in phase 3 overall survival spark FDA hold on Oncopeptides' multiple myeloma drug

This is not the first time the FDA has found itself warning of a cancer therapy’s potential detrimental effect to patients based on findings from a confirmatory clinical trial. The agency last year flagged that patients with previously untreated triple-negative breast cancer performed worse on a combination of Tecentriq and the chemotherapy paclitaxel than they did on chemotherapy alone. The findings were from the phase 3 IMpassion131 trial, which was supposed to confirm an accelerated nod for the combination of Tecentriq with Abraxane, or nab-paclitaxel, in PD-L1-positive TNBC.

Failure to show a survival benefit in a confirmatory trial has led to market withdrawals before—let alone an increased risk of death. In 2019, Eli Lilly pulled its sarcoma drug Lartruvo after a confirmatory phase 3 trial showed that adding the drug to chemotherapy didn’t prolong patients’ lives. The drug won its conditional nod in 2016 based on a smaller trial.

RELATED: Bristol Myers, yielding to FDA pressure, pulls Opdivo in post-Nexavar liver cancer

The Pepaxto snafu is another blow to the FDA’s accelerated approval program, which is designed to get novel drugs to patients faster, typically based on surrogate trial markers. The program was put under public spotlight in the wake of the FDA’s controversial approval of Biogen’s Alzheimer’s disease drug Aduhelm.

Drug reviewers at the FDA have recently conducted an industrywide review of accelerated approvals of immuno-oncology agents that have failed in confirmatory trials. That campaign has led to voluntary withdrawals of six indications for PD-1/L1 inhibitors.

Editor's Note: The story has been updated with a new headline to reflect that the FDA is only raising the possibility of potential market removal of Pepaxto.