Despite being approved in Europe, Oncopeptides' Pepaxto will remain sidelined in the US

In an FDA advisory committee meeting on Thursday afternoon, few punches were pulled as oncology experts assessed Oncopeptides’ multiple myeloma treatment Pepaxto (melflufen).

The drug won approval in February of 2021 under the FDA’s controversial accelerated pathway but was pulled off the U.S. market eight months later when data from a confirmatory trial indicated that it might do more harm than good.

“How the heck would I give informed consent to a patient to receive this drug?” Mikkael Sakeres, M.D., a former chair of the committee, now at the University of Miami, asked during the meeting.

But Pepaxto is alive and well in Europe, where it won approval in June based on the same data that the committee reviewed on Thursday. The difference is the regulatory acceptance of Oncopeptides’ interpretation of the trial results.

“There are different regulatory environments but fundamentally science is science,” Oncopeptides CEO Jakob Lindberg said in an interview after the adcomm. “Gravity should apply on both sides of the pond.”

In the Ocean-3 trial, the death rate for Pepaxto was 47.6%, versus 43.4% for Bristol Myers Squibb’s Pomalyst (pomlidomide), the control arm. Meanwhile, the median duration of survival was 19.7 months for those on Pepaxto versus 25 months for Pomalyst.

The Swedish-based company however says a subgroup analysis shows that Pepaxto has value. Oncopeptides pointed to positive results when eliminating a key patient group—those who had undergone stem-cell transplants within the last three years.

The company also says age is a major separator. While Pomalyst performs better on younger patients, Pepaxto is a superior option for those who are elderly.

“It’s an astonishingly heterogenous survivor result,” Lindberg said. “You have almost twice the survival on melflufen compared to pomalidomide in the elderly and almost twice the survival with pomalidomide over melflufen in the young.”

At the urging of the FDA, the committee rejected this subgroup analysis to the tune of a 14-2 vote. FDA oncology czar Richard Pazdur, M.D., blasted Oncopeptides for its “post hoc” approach.

“When you have people resubmitting data and changing analysis, this could bring up issues of study conduct and integrity of the study,” Pazdur said. “They have to demonstrate with substantial evidence, efficacy. It is not our responsibility to disprove something.”

In retrospect, Lindberg said that the company and the FDA never found “a good way to collaborate and have a good scientific dialogue.”

“It was almost like there was bad blood,” Lindberg said of the adcomm.

The session was another example of why harsh scrutiny has fallen upon accelerated approvals following the FDA’s ill-fated green light for Biogen’s Alzheimer’s drug Aduhelm.

The process was designed to speed promising drugs to the market and save lives. But in the case of Pepaxto, the drug has proven to be less than advertised.

“Given what is currently known, we would not have granted accelerated approval as we cannot conclude melflufen provides a meaningful benefit over existing therapies,” FDA clinical reviewer Alexandria Schwarsin, M.D., said during the meeting.

Lindberg said it would take three to four years to conduct another trial. Meanwhile, Pepaxto will be on different development stages in the United States and Europe. The launch of Pepaxti—as it is known in Europe—begins in October.

“It would be interesting if we wrote some regulatory history here,” Lindberg said with a laugh. “Where the same dataset results in full approval in one geography and then we have product withdrawal due to safety concerns in the other. It would be like, OK, that will be a first.”