The US Food and Drug Administration (FDA) has requested that Oncopeptides AB withdraw the US marketing authorization for its multiple myeloma drug Pepaxto (melphalan flufenamide), the company announced in a press release.

The drug was granted an accelerated approval by the FDA in February 2021, for use in combination with dexamethasone in adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy.

However, a confirmatory trial to show clinical benefit raised concerns about safety.

This was the phase 3 OCEAN study, which showed a higher mortality associated with melphalan flufenamide in the experimental arm compared with pomalidomide (Pomalyst) in the comparator arm.

The FDA already flagged this issue last year. In July 2021, the FDA issued a safety alert flagging the increased risk for death observed in the OCEAN trial among patients receiving melphalan flufenamide vs pomalidomide (47.6% vs 43.4%) and a 5.3-month shorter overall survival.

The issue was also discussed in September 2022 by FDA’s Oncologic Drugs Advisory Committee, which voted 14-to-2 against maintaining the accelerated approval. As reported by Medscape Medical News, the committee cited an unfavorable risk/benefit profile.

The company stopped marketing the drug in the United States in October 2021 at the FDA’s request but continued to make it available for patients already undergoing treatment.

However, in March 2022, Oncopeptides rescinded the letter that voluntarily withdrew the agent from market, after further review of overall survival data from the OCEAN trial led the company to reconsider its decision. Notably, marketing efforts were still discontinued while the company worked with the FDA to interpret the data, it stated in the press release.

That review of the data showed that progression-free survival was 42% higher with melphalan flufenamide vs pomalidomide and overall response rates were 32.1% vs 26.5%, respectively.

Now, the FDA has requested that the company withdraw its US marketing authorization.

“We respect FDA’s accelerated approval regulations,” Jakob Lindberg, CEO of Oncopeptides commented in the press release.

However, he also added, “Multiple myeloma remains an incurable disease, and the treatment options for patients with triple class refractory disease will ultimately become exhausted. The OCEAN study demonstrated clinical benefit for multiple myeloma patients, in particular for non-transplanted elderly patients where the unmet medical need remains very high.”

Commercialization of the drug in Europe, under the brand name Pepaxti, is ongoing.

“Pepaxti has a full approval from the European Medicines Agency, EMA, since August 18, 2022, and was approved by the Medicines and Healthcare Products Regulatory Agency, MHRA, in the UK on November 11, 2022,” the company noted.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at [email protected] or on Twitter: @SW_MedReporter

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