Why Oncopeptides Withdrew its FDA Application for Melflufen (PEPAXTO) in Multiple Myeloma
Oncopeptides AB has decided to withdraw their US FDA application for melflufen, but will continue to support myeloma patients currently on the drug.
The company received FDA accelerated approval for melflufen in February of this year based on the results of the HORIZON trial which showed a 23.7% Overall Response Rate for the melflufen/dex combination. The HORIZON trial was a single arm trial testing melflufen/dex in highly relapsed patients.
The accelerated approval was contingent on results of the OCEAN trial; a head-to-head study which compared pomalidomide/dex vs. melflufen/dex, which were expected to confirm the HORIZON trial's results. In July, the OCEAN trial results presented at the IMW conference showed a slight increase in deaths in the melflufen/dex arm compared to the pomalidomide/dex arm with a hazard ratio of 1.06 (a hazard ratio over 1 shows statistical significance in favor of the standard of care).
Based on those results, the FDA issued an alert and put a hold on current melflufen clinical trials, which prevented any new patients from joining, although patients who were doing well on study could continue on study.
Interestingly, the OCEAN study data presented by Fredrik Schjesvold, MD, head of the Oslo Myeloma Center at the University of Oslo, showed that the melflufen/dex combination was superior to pomallidomide/dex for patients without prior stem cell transplant (9.3 months vs. 4.6 months). The data also indicated that it was helpful in patients who were out 5 years from stem cell transplant.
Although melflufen/dex was superior to pomalidomide/dex in these subset patient populations, the FDA indicated to the company that it would not consider these results to confirm the HORIZON data and that the subset population was too small to consider it as an unmet need. Oncopeptides AB made the difficult decision to withdraw the melflufen US FDA application and close their US business unit. The decision was not based on any new data since July, but on their ongoing conversations with the FDA.
“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," says Marty J Duvall, Chief Executive Officer at Oncopeptides. “The Company now needs to refocus its resources and energy on R&D 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.”
The Swedish-based company will continue to develop a related peptide conjugate called OPD-5 which would replace melphalan as part of the stem cell transplant process.
For myeloma patients currently using melflufen, Oncopeptides will continue to provide the drug. No new patients will be prescribed melflufen in the United States.