The U.S. Food and Drug Administration (FDA) pulled its initial approval of Oncopeptides’ Pepaxto (melphalan flufenamide), a medication used in combination with corticosteroid dexamethasone to treat certain multiple myeloma cases.
The final decision to withdraw approval was made on Feb. 23, approximately three years after the drug received accelerated approval for treating patients with multiple myeloma who had received four or more prior lines of therapy and whose cancer had not responded to at least one proteasome inhibitor, immunomodulatory agent, or CD38-directed monoclonal antibody.
The decision was issued by the FDA’s Center for Biologics Evaluation and Research Director Dr. Peter Marks, the commissioner’s designee, the FDA reported.
This event marks the first time the FDA has used its amended procedures, enacted in 2023, to withdraw accelerated approval medications. As part of the new procedures, the FDA provided Oncopeptides with a notice of the proposed withdrawal of approval, an explanation, and an opportunity for a meeting with and written appeal to the commissioner. The drug manufacturer submitted an appeal and met with the commissioner’s designee.
Manufacturer Appeals Decision
In its written appeal, Oncopeptides noted that its original study “remains compelling evidence of the drug’s efficacy and safety in this serious and life-threatening disease” and that the “post-marketing study … met the primary endpoint of progression-free survival.”
According to the FDA, the initial approval was based on a single-arm phase 2 study. However, in a phase 3 study, trial results on the combination of Pepaxto and dexamethasone failed to achieve pre-specified improvement in progression-free survival rates; in fact, the combination of medications had a detrimental effect on patients. This lack of efficacy, combined with a vote from the Oncology Drugs Advisory Committee in opposition to the use of the drug, pushed the Center for Drug Evaluation and Research to initiate the process of approval withdrawal on July 7, 2023.
The company stopped marketing the drug to new patients in October 2021 in the United States at the request of the FDA but continued to make it available to patients already taking it.
When the post-marketing study results came out, indicating that overall survival rates worsened in patients taking the medication, the company pulled the medication altogether in the United States.
“We respect FDA’s accelerated approval regulations,” Jakob Lindberg, former CEO of Oncopeptides, said in 2022. “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.”
Pepaxto Still Used in Europe
Multiple myeloma, a cancer that forms in plasma cells, is a major cause of cancer morbidity and mortality in the United States. The FDA reported an estimated 35,730 cases and 12,590 deaths in 2023. Available treatments include chemotherapy, immunotherapies, and autologous hematopoietic stem cell transplant (HSCT). None of these cures the cancer, however, and patients tend to relapse and need additional therapies. As such, the FDA recognizes the need for safe and effective treatments.
The drug is still on the market in Europe. Pepaxto was granted approval for use in Iceland, Liechtenstein, and Norway in August 2022 and the United Kingdom in November 2022, according to the manufacturer. Patients must have undergone three types of therapies that failed to treat their cancer to be eligible for treatment with the drug. Additionally, patients must be at least three years removed from a stem cell transplantation.
Although the drug is no longer available in the United States, European regulators have seemingly embraced it. The drug just received a five-year extension on the European market, the company announced.
“The extended exclusivity on the European market for Pepaxti (Pepaxto’s brand name in Europe) creates added opportunity for Oncopeptides, and we look forward to being able to continue serving the high unmet need for patients suffering from relapsing, refractory multiple myeloma for even longer, which we believe could create significant benefits for both patients and our shareholders,” Sofia Heigis, current CEO of Oncopeptides, said in a press release.