FDA publishes Oncopeptides’ withdrawal appeal for Swedish biotech’s cancer drug Pepaxto

Oncopeptides’ appeal to the FDA’s withdrawal proposal for the blood cancer drug Pepaxto has been made public, shedding new light on the seesawing that’s been going on at the Swedish biotech.

Pepaxto has been on a rocky journey since its accelerated approval in early 2021 for use in combination with dexamethasone as a fifth-line treatment for adults with relapsed or refractory multiple myeloma. The FDA alerted patients in the summer of 2021 that the confirmatory trial was halted after concerns of increased risk of death in patients taking a combination of Pepaxto (melphalan flufenamide) and dexamethasone. FDA’s reviewers concluded that a confirmatory trial did not show safe and efficacious treatment benefit.

Jakob Lindberg

The biotech withdrew the drug from the market, then reneged on that decision, and then FDA’s outside oncology advisors overwhelmingly voted against the drug’s benefit-risk profile. Then-CEO Jakob Lindberg told Endpoints News last December the biotech was “leaning toward” complying with the withdrawal request.

In July, the Center for Drug Evaluation and Research notified Oncopeptides of its proposal for a swift withdrawal of Pepaxto, saying the drug failed the primary endpoint of progression-free survival.

“The Sponsor contends that PFS superiority was met based on reassessment of 29 patients after the primary database lock. CDER disagrees that consideration of the post-hoc revised analyses is appropriate, but, even if it were, the treatment effect estimates with respect to the difference in median PFS did not exceed 2 months, which is low,” according to a memo written by Division of Hematologic Malignancies II director Nicole Gormley.

And then in August, Oncopeptides again reverted plans and submitted an appeal to the expedited withdrawal proposal from FDA.

In its appeal, posted this week, Oncopeptides lambasted the FDA’s interpretation of the trial results, claiming the agency’s analysis is “not scientifically correct.”

“The Sponsor is acutely aware how banal it might sound that the OP-103 study result is explained by the comparator arm. However, in this very unusual case it is true. In addition to being important for the interpretation of study OP-103 results and conclusions regarding melflufen’s benefit, this finding has significant implications for the correct use of IMiD-based [immunomodulatory drug] therapy in multiple myeloma patients,” Oncopeptides wrote in its appeal. “This is the reason why the Sponsor has persisted in our attempts at changing the Agency’s view of study OP-103 results and the reason for this appeal to Notice of Proposed Withdrawal dated July 7, 2023.”

The appeal will be decided by Peter Marks, the director of FDA’s Center for Biologics Evaluation and Research. He’ll take into account public comments on the withdrawal proposal, which can be submitted until Sept. 25.

Sofia Heigis

“Our OCEAN study demonstrated clinical benefit for multiple myeloma patients, in particular for non-transplanted elderly patients where the unmet medical need remains very high, and we remain confident that it would provide value for patients all over the world, including the U.S.,” Oncopeptides CEO Sofia Heigis said in a statement. “We value the opportunity to share our perspective and look forward to a continued dialogue with the FDA.”

The company said it has “strong confidence in the product” and reminded investors that they “currently don’t market Pepaxto in the U.S.”

“Oncopeptides’ full strategic focus is on the product roll-out in Europe, where we have a marketing authorization and an established marketing company,” the biotech wrote in a statement.

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