FDA Requests Melphalan Flufenamide be Withdrawn From US Market


The FDA has now requested that the manufacturer of melphalan flufenamide withdraw the multiple myeloma drug from the United States market months after the drug developer rescinded a letter voluntarily withdrawing the therapeutic.

The FDA has requested that the marketing authorization for melphalan flufenamide (Pepaxto) be withdrawn from the United States market following confirmatory findings from the phase 3 OCEAN trial (NCT03151811), according to a press release from Oncopeptides AB.1

Data from the OCEAN 3 trial indicated the hazard ratio for overall survival by independent review committee in the intent-to-treat population was 1.104 (95% CI, 0.846-1.441), with notable differences in survival findings for both melphalan flufenamide in the experimental arm and pomalidomide (Pomalyst) in the comparator arm across a number of patient subgroups.

“We respect FDA´s accelerated approval regulations,” Jakob Lindberg, CEO of Oncopeptides, said in a press release. “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.”

The FDA granted accelerated approval to melphalan flufenamide to treat adults with relapsed/refractory multiple myeloma following at least 4 lines of therapy.2

The February 2021 decision was based on data from the phase 2 HORIZON trial (NCT02963493), which assessed melphalan flufenamide in combination with dexamethasone in relapsed/refractory multiple myeloma. At the time, investigators reported an overall response rate (ORR) of 23.7% (95% CI, 15.7%-33.4%) with a median duration of response of 4.2 months (95% CI, 3.2-7.6) in a subpopulation of 97 patients who received 4 or more prior lines of therapy.

However, in September 2022, the FDA’s Oncologic Drugs Advisory Committee gave a 14-to-2 vote against maintaining the accelerated approval for melphalan flufenamide after determining that it had an unfavorable risk/benefit profile.3

Oncopeptides AB made the decision to withdraw melphalan flufenamide from the United States market following the release of confirmatory results from the OCEAN trial with the intent of working with the FDA to continue providing the agent for those who were still undergoing treatment.4

However, in March 2022, Oncopeptides rescinded the letter that voluntarily withdrew the agent from market after further review of OS data from the OCEAN trial led the company to reconsider its decision.5 Notably, marketing efforts were still discontinued while the company worked with the FDA to interpret the data.

Other findings from the OCEAN trial indicated that melphalan flufenamide yielded a progression-free survival that was 42% higher vs pomalidomide by investigator and IRC assessment (HR,0.817; 95% CI, 0.659-1.012; P = .064; HR, 0.790; 95% CI, 0.639-0.976).

Additionally, the overall response rate was 32.1% vs 26.5% in the melphalan flufenamide and pomalidomide arms, respectively.


  1. Oncopeptides provides update on Pepaxto US marketing authorization. News release. Oncopeptides AB. December 7, 2022. Accessed December 9, 2022. https://bit.ly/3YcSMuG
  2. FDA grants accelerated approval to melphalan flufenamide for relapsed or refractory multiple myeloma. News release. FDA. February 26, 2022. Accessed December 9, 2022. https://bit.ly/3SeTdl1
  3. Oncologic Drugs Advisory Committee (ODAC) Meeting, September 22-23, 2022 (Day 1). Streamed live September 22, 2022. Accessed December 9, 2022. https://bit.ly/3LNcW9a
  4. Oncopeptides withdraws Pepaxto® in US, scale down organization and focus on R&D. News release. Oncopeptides AB. October 22, 2021. Accessed December 9, 2022. https://bit.ly/3B5OCIC
  5. Important information regarding PEPAXTO® in the United States. News release. Oncopeptides. March 1, 2022. Accessed December 16, 2022. https://bit.ly/3hq2VUE

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