Melphalan flufenamide withdrawn from the US market following a speech with the FDA



Following discussions with the FDA, INN melphalan flufenamide was withdrawn from the market in the United States based on data from the Phase 3 OCEAN study.

Drug developer Oncopeptides AB has made a decision to withdraw INN melphalan flufenamide (Pepaxto) from the US market in light of the results of the phase 3 OCEAN trial (NCT03151811); however, Oncopeptides and the FDA intend to continue to work together to ensure that the agent will be available to people currently being treated with melphalan flufenamide.1

The results of the trial, which evaluated melphalan flufenamide in combination with dexamethasone versus pomalidomide (Pomalyst) / dexamethasone in relapsed / refractory multiple myeloma, showed that overall survival (OS) with the experimental design was not improved compared to the control, with a risk ratio of 1.104 (95% CI, 0.846-1.441). Following conversations with the FDA, it was determined that the OCEAN data did not meet the criteria for a confirmatory trial. Notably, Oncopeptides said the data was, in fact, scientifically significant and warranted further investigation.

As a result of these developments, the company plans to reduce and focus on research and development in order to focus on the development of its proprietary peptide and drug conjugate platform.

“The decision to take Pepaxto off the market was a difficult one, which was taken with great consideration and with the best intentions for patients and shareholders,” said Marty J. Duvall, CEO of Oncopeptides, in a statement. Press release. “The Company must now refocus its resources and energy on [research and development] and stay true to its mission of bringing hope to patients through science. We believe this is the only viable path to achieve this goal. “

Results of the OCEAN study reported that melphalan flufenamide gave independent review committee (IRC) non-inferior progression-free survival (PFS) compared to pomalidomide (RR: 0.817, 95% CI: 0.659-1.012; P = .064).2 When PFS was assessed by investigator assessment, the risk ratio favored the investigational agent (RR: 0.790; 95% CI: 0.639-0.976). In addition, the median PFS was 42% higher in the melflufen flufenamide arm compared to pomalidomide by both investigator and CRF. Investigators reported overall response rates of 32.1% and 26.5% in both arms, respectively.

In July 2021, the The FDA has partially suspended all clinical trials using melphalan flufenamide following updated OCEAN results. Despite meeting its primary endpoint of superior PFS by an independent review committee, the investigators reported that the secondary endpoint of overall survival (OS) was in favor of the control group. Partial clinical suspension was implemented until further research could confirm a sufficiently large difference in OS between specific patient subgroups.

“We remain confident in our science platform, despite the fact that OCEAN data has not cleared regulatory hurdles to confirm expedited approval in the United States,” concluded Jakob Lindberg, Scientific Director of Oncopeptides. “In the future, we will further explore our [Peptide Drug Conjugate]–Platform, to develop drugs that can potentially make a significant difference for patients. Oncopeptides is committed to working closely with regulatory authorities to assess the most appropriate possibilities for our pipeline products.

Melphalan flufenamide obtained accelerated authorization in February 2021.

The references

  1. Oncopeptides withdraws Pepaxto® in the United States, reduces its organization and focuses on R&D. Press release. Oncopeptides AB. October 22, 2021. Accessed October 22, 2021.
  2. Oncopeptides AB: The OCEAN phase 3 study shows that melflufen is at least as effective as pomalidomide, the most widely used drug in relapsed refractory multiple myeloma. Press release. Oncopeptides AB. May 25, 2021. Accessed May 25, 2021.


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