Oncopeptides has decided to withdraw Pepaxto (melphalan flufenamide) from the US market after interactions and dialogue with the US Food and Drug Administration (FDA) and following the announcement of the phase III OCEAN study (NCT03151811) results () which did not meet the criteria of a confirmatory study. Oncopeptides will refocus and return to being a Sweden based R&D company, dedicated to further explode its proprietary PDC platform.
Pepaxto was granted accelerated approval in the US for the treatment of relapsed or refractory multiple myeloma (RRMM) patients who have received at least four prior lines of therapy on February 26th, 2021 based on the results from the phase II HORIZON study (NCT02963493; ). Oncopeptides was required to conduct the OCEAN study as a post-approval requirement under the accelerated approval program.
On July 8th, 2021, the FDA requested the partial clinical hold of all clinical studies with melflufen based on the Overall Survival (OS) data from the OCEAN study. The OS HR was 1.104 in favor of pomalidomide (study comparator). On July 28th, the FDA issued a safety alert to patients and health care professionals, regarding an increased risk of death associated with Pepaxto in the OCEAN study. The decision of Pepaxto withdrawal came six days before an FDA advisory committee was set to discuss the safety findings from the OCEAN study.
The company said that it will work together with the FDA to continue to make the drug available for patients currently treated with Pepaxto. Additionally, and despite Pepaxto’s clinical program still being on clinical hold, Oncopeptides believes that the OCEAN data are meaningful and that the findings warrant further evaluation. The OS trended in favour of melflufen in patients without a prior ASCT, and favoured pomalidomide in patients with a prior ASCT; could there be a path for non-transplanted patients?
Oncopeptides will immediately refocus the company and return to being a Sweden based R&D company, dedicated to further develop our proprietary Peptide Drug Conjugate (PDC) platform including the next generation of drug candidates including OPD5 and OPDC3. The organization will be scaled down to increase our cash runway and focus on building a platform for longer term development and growth. As a consequence, the commercial business units in the US and Europe will be closed down and the Stockholm based organization will be significantly reduced. The application to the European Medicines Agency, EMA, for a potential Conditional Marketing Authorization of melflufen in the EU, based on the pivotal phase 2 HORIZON study in relapsed refractory multiple myeloma, remains pending. The company expects to receive a CHMP opinion in Q2, 2022.