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  4. FDA issues final decision to withdraw approval of Pepaxto (melphalan flufenamide)
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FDA issues final decision to withdraw approval of Pepaxto (melphalan flufenamide)

Pepaxto Update [2/23/2024] Today, FDA announced its final decision to withdraw approval of Pepaxto (melphalan flufenamide), which was approved for use in combination with dexamethasone to treat certain patients with multiple myeloma.    

The agency determined the following grounds for withdrawal were met: (1) the confirmatory study conducted as a condition of accelerated approval did not confirm Pepaxto’s clinical benefit, and (2) the available evidence demonstrates that Pepaxto is not shown to be safe or effective under its conditions of use.  

The final decision was issued by FDA’s Center for Biologics Evaluation and Research Director Peter Marks, M.D., Ph.D., as the Commissioner’s designee. The decision is effective immediately. FDA plans to publish a Federal Register notice announcing the availability of today’s decision and remove Pepaxto from the Orange Book. It is FDA’s understanding that Oncopeptides does not currently market Pepaxto in the U.S. 

This is the first time FDA has used the amended procedures for withdrawal of accelerated approval that were enacted in 2023, as part of the Food and Drug Omnibus Report Act of 2022 (FDORA). In accordance with the new procedures, FDA provided Oncopeptides with a notice of proposed withdrawal of approval, an explanation for the proposed withdrawal, and an opportunity for a meeting and a written appeal to the Commissioner (or designee). Oncopeptides submitted a written appeal and met with the Commissioner’s designee. This decision is FDA’s response. See the public docket for more information. 

FDA alerts patients and health care professionals about clinical trial results showing an increased risk of death associated with Pepaxto (melphalan flufenamide)

Pepaxto Update [8/24/2023] FDA’s Center for Drug Evaluation and Research (CDER) has provided Oncopeptides AB (Oncopeptides) notice of its proposal to withdraw accelerated approval of Pepaxto (melphalan flufenamide) because the post-approval confirmatory trial required as a condition of Pepaxto’s approval failed to verify clinical benefit and available evidence demonstrates Pepaxto is not shown to be safe or effective under its conditions of use. 

An Oncologic Drugs Advisory Committee (ODAC) was held on September 22, 2022, to discuss the results of the OCEAN confirmatory trial and the benefit-risk profile of Pepaxto for the indicated population. The ODAC voted 14 to 2 that the benefit-risk profile of melphalan flufenamide was not favorable for the currently indicated patient population, given the results of the OCEAN confirmatory trial. Materials from this September 22, 2022, ODAC meeting are available here. 

Pepaxto is not currently being marketed in the United States as indicated in FDA’s publication, Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations.

Pepaxto Update [7/28/2021] FDA is alerting patients and health care professionals that a clinical trial (OCEAN, Study OP-103) evaluating Pepaxto (melphalan flufenamide) with dexamethasone to treat patients with multiple myeloma showed an increased risk of death.

The trial compared Pepaxto with low-dose dexamethasone to pomalidomide with low-dose dexamethasone in patients with relapsed or refractory (resistant) multiple myeloma following 2-4 lines of prior therapy and in patients who were resistant to lenalidomide in the last line of therapy.

FDA encourages health care professionals to review patients’ progress on Pepaxto and discuss the risks of continued administration with each patient in the context of other treatments. Patients currently receiving Pepaxto should also discuss with their health care professional the risks and benefits of receiving Pepaxto.

In February 2021, FDA approved Pepaxto under Accelerated Approval for use in combination with dexamethasone to treat adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody. The manufacturer, Oncopeptides AB, was required to conduct the OCEAN trial as a post-approval requirement under the accelerated approval program.

Due to the detrimental effect on overall survival in the OCEAN trial, FDA is requiring the manufacturer suspend enrollment in the trial. FDA has also suspended enrollment in other ongoing Pepaxto clinical trials. Patients receiving clinical benefit from Pepaxto may continue treatment in the OCEAN trial provided they are informed of the risks and sign a revised written informed consent.

FDA continues to evaluate the OCEAN trial results and may hold a future public meeting to discuss these safety findings and explore the continued marketing of Pepaxto. The agency will update patients and health care professionals when new information is available.

FDA encourages health care professionals and patients to report adverse events or quality problems experienced with the use of any medication to FDA’s MedWatch Adverse Event Reporting program: 

  • Complete and submit the report online; or
  • Download and complete the form, then submit it via fax at 1-800-FDA-0178

Statistical Analysis Results from OCEAN, Study OP-103 (PDF-134KB)

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