Melphalan Flufenamide Withdrawn From US Market Following Discourse With FDA

Following discussion with the FDA, INN melphalan flufenamide has been withdrawn from market in the United States based on data from the phase 3 OCEAN study.

Drug developer Oncopeptides AB has made the decision to withdraw INN melphalan flufenamide (Pepaxto) from market in the United States in light of findings from the phase 3 OCEAN trial (NCT03151811); however, Oncopeptides and the FDA intend to continue working together to ensure the agent will be available for those currently undergoing treatment with melphalan flufenamide.1

Findings from the trial, which assessed melphalan flufenamide in combination with dexamethasone vs pomalidomide (Pomalyst)/dexamethasone in relapsed/refractory multiple myeloma, highlighted that overall survival (OS) with the experimental regimen was not improved versus the control, with a hazard ratio of 1.104 (95% CI, 0.846-1.441). Following conversations with the FDA, it was determined that data from OCEAN did not meet the criteria for a confirmation trial. Notably, Oncopeptides stated that the data were, in fact, scientifically meaningful and deserving of further investigation.

Due to these developments, the company plans to scale down and shift its focus to research and development in order to focus on developing their proprietary peptide drug conjugate platform.

“The decision to withdraw Pepaxto from the market has been a difficult decision, that has been made with great consideration and with the best intentions for patients and shareholders,” Marty J. Duvall, chief executive officer at Oncopeptides, said in a press release. “The Company now needs to refocus its resources and energy on [research and development] and remain true to its mission of bringing hope to patients through science. We believe that this is the only viable path forward to accomplish this goal.”

Findings from the OCEAN study indicated that melphalan flufenamide yielded noninferior progression-free survival (PFS) by independent review committee (IRC) compared with pomalidomide (HR, 0.817, 95% CI, 0.659-1.012; P = .064).2 When PFS was evaluated by investigator assessment, the hazard ratio favored the experimental agent (HR, 0.790; 95% CI, 0.639-0.976). Moreover, the median PFS was 42% higher in the melflufen flufenamide arm vs pomalidomide by both investigator and IRC. Investigators reported an overall response rates of 32.1% and 26.5% in both arms, respectively.

In July 2021, the FDA put a partial clinical hold on all trials utilizing melphalan flufenamide following updated results from OCEAN. Despite meetings its primary end point of superior PFS by independent review committee, investigators reported the secondary end point of overall survival (OS) was in favor of the control group. The partial clinical hold was put in place until further research could confirm a large enough difference in OS between specific patient subgroups.

“We remain confident in our scientific platform, despite the fact that the OCEAN data didn´t pass the regulatory hurdles to confirm the accelerated approval in the US,” Jakob Lindberg, chief scientific officer at Oncopeptides, concluded. “Going forward we will further explore our [Peptide Drug Conjugate]–platform, to develop drugs that potentially can make a significant difference for patients. Oncopeptides is committed to work closely with the regulatory authorities to evaluate the most appropriate possibilities for our pipeline products.”

Melphalan flufenamide was granted an accelerated approval in February 2021.


  1. Oncopeptides withdraws Pepaxto® in US, scale down organization and focus on R&D. News release. Oncopeptides AB. October 22, 2021. Accessed October 22, 2021.
  2. Oncopeptides AB: Phase 3 OCEAN study demonstrates that melflufen is at least as efficacious as pomalidomide, the most used medicine in relapsed refractory multiple myeloma. News release. Oncopeptides AB. May 25, 2021. Accessed May 25, 2021.