FDA Grants Priority Review to Melflufen for Myeloma

The FDA granted priority review to a new drug application for INN melphalan flufenamide, or melflufen, in combination with dexamethasone for the treatment of adults with multiple myeloma (MM) whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody, or is triple-class refractory.

The investigational agent is a peptide-drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells.

The application is supported by results from the single-arm, open label phase II HORIZON study of intravenous melflufen in adults with MM whose disease is triple-refractory. Patients received melflufen 40 mg and dexamethasone 40 mg on days 1, 8, 15, and 22 of each 28-day cycle. According to the manufacturer and study sponsor, Oncopeptides AB, the combination treatment demonstrated encouraging efficacy and a manageable safety profile in heavily pretreated patients. Hematologic adverse events (AEs) were the most commonly reported AEs, and there was a low incidence of non-hematologic AEs.

OCEAN, a randomized, controlled, open-label phase III trial of melflufen, is currently enrolling patients and will review the efficacy of melflufen plus dexamethasone versus that of a combination of pomalidomide and dexamethasone.

A target date for review of the new drug application has been set for February 28, 2021.

Sources: Oncopeptides AB press release, August 29, 2020; ClinicalTrials.gov, “A Study of Melphalan Flufenamide (Melflufen) in Combination With Dexamethasone in Relapsed Refractory Multiple Myeloma Patients (HORIZON).”