On March 1, the U.S. Food and Drug Administration (FDA) granted accelerated approval to melphalan flufenamide (melflufen) in combination with dexamethasone for the treatment of relapsed/refractory (RR) multiple myeloma (MM).
Melflufen, sold commercially as PEPAXTO, is the first peptide-drug conjugate approved for the treatment of MM. The newly approved therapeutic combination has been designated for the treatment of adults with RRMM who have received at least four prior therapies and are triple-class refractory to at least one proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody.
The FDA’s decision is supported by data from the phase II HORIZON study, which evaluated intravenous melflufen with dexamethasone in 157 patients with heavily pretreated RRMM, of whom 97 were triple-class refractory. The overall response rate was 23.7%, with a median progression-free survival (PFS) of 4.2 months. Among patients who achieved at least a partial response, median PFS was 8.5 months. Median overall survival was 11.6 months. The most common adverse events, occurring in more 20% of patients, were fatigue, nausea, diarrhea, pyrexia, and respiratory infection.
“We are proud to bring forward the first anticancer peptide-drug conjugate approved by the FDA for MM,” said Jakob Lindberg, chief scientific officer at Oncopeptides, the drug’s manufacturer, in a press release. “PEPAXTO uses innovative technology that links a peptide carrier to a cytotoxic agent. The conjugated agent is a highly lipophilic compound, which allows it to be rapidly distributed into cells. The compound then leverages amino peptidases that are overexpressed in MM cells, causing the release of the cytotoxic payload.”
“Moving ahead, our focus is to further advance PEPAXTO. We look forward to receiving top line data from the phase III OCEAN study in the second quarter,” said Oncopeptides CEO Marty Duvall. “This comparative study is designed to support a future supplementary New Drug Application to expand the label.”