Oncopeptides disagrees with the FDA about Pepaxto and will make a decision about next steps by the end of the first quarter of 2023.
The FDA has requested that Oncopeptides voluntarily withdraw the indication for Pepaxto (melphalan flufenamide, also called melflufen). The request is based on the outcome of the confirmatory phase 3 OCEAN study, which demonstrated an overall survival hazard ratio of 1.1 in the intent to treat population. A hazard ratio of more than 1 indicates a risk of harm.
But a company spokesperson told Formulary Watch that Oncopeptides disagrees with the agency´s assessment of the data from the OCEAN study and has not withdrawn the U.S. indication. “We will carefully consider what is the best option for the patients and the company. We expect a decision to be made before end of Q1, 2023,” the spokesperson said.
Pepaxto has had a difficult path toward full approval. The therapy had been granted accelerated approval in the United States on Feb. 26, 2021, to be used in combination with dexamethasone to treat adult patients with relapsed or refractory multiple myeloma. It is indicated for those who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody. The approval was based on the OP-106 (HORIZON) trial, a single-arm trial. The overall response rate (ORR) was 23.7% with a median duration of response (DOR) of 4.2 months.
At the FDA’s request, Oncopeptides stopped marketing Pepaxto in the United States on Oct. 22, 2021, and Pepaxto is currently not commercially available for U.S. patients. And in September 2022, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 14 to 2 against Pepaxto. Committee members agreed with the FDA that OCEAN demonstrated a worse overall survival and failed to verify clinical benefit. The agency also indicated that the dose of Pepaxto was not optimized to support a favorable benefit-risk profile. The FDA disagreed with Oncopeptides analysis of the efficacy data, saying it relied heavily on post hoc sub-group analyses. Subgroup analyses, regulators said, should be used for exploratory or hypothesis-generating purpose and are not meant to provide conclusive evidence of efficacy and safety.
In a press release, the company said Pepaxto demonstrated significant survival differences for both melflufen and the comparator drug pomalidomide for large relevant patient groups. “Multiple myeloma remains an incurable disease, and the treatment options for patients with triple class refractory disease will ultimately become exhausted,” Jakob Lindberg, chief executive officer of Oncopeptides said. “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."
Pepaxti has a full approval from the European Medicines Agency since Aug. 18, 2022, and was approved by the Medicines and Healthcare Products Regulatory Agency in the United Kingdom on Nov. 11, 2022. Both approvals take the large OCEAN study overall survival differences across relevant patient groups into account, the company said.