FDA Approves Melphalan Flufenamide Combo for Triple-Refractory Myeloma

The FDA approved melphalan flufenamide (Pepaxto; melflufen) plus dexamethasone for adults with triple-refractory multiple myeloma.

The FDA has approved melphalan flufenamide (Pepaxto; melflufen) plus dexamethasone for adults with multiple myeloma whose disease is refractory to 1 or more of each type of agent: proteasome inhibitor (PI), immunomodulary agent (IMiD), and anti-CD38 monoclonal antibody.

“Melphalan flufenamide is a novel and innovative therapeutic option which is active in patients with multiple myeloma who have a refractory disease, and the product has a manageable toxicity”, says Professor Ola Landgren, Chief of Myeloma Program and Leader of Experimental Therapeutics Program, Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami Health System in Miami, Florida, in a press release. “Melphalan flufenamide will complement existing treatment regimens and contribute to address the growing unmet medical need among patients with relapsed or refractory multiple myeloma.”

The approval is based on findings from the phase 2 HORIZON trial, in which melphalan flufenamde combination elicited a 23.7% overall response rate, with a median duration of response of 4.2 months. The regimen also showed activity in patients with extramedullary disease (41%).

HORIZON included 157 patients with relapsed/refractory multiple myeloma who had 2 or more prior lines of therapy, and were exposed to an IMiD and a PI and were refractory to pomalidomide (Pomalyst) and/or daratumumab (Darzalex). Participants in the study had triple-class refractory disease and/or extramedullary disease (EMD) and/or high-risk cytogenetic features. Their ECOG performance status had to fall between 0 and 2.

Patients enrolled in HORIZON were administered 40 mg of melphalan flufenamide and 40 mg of dexamethasone on day 1, and then 40 mg of dexamethasone on days 8 and 15. Patients who were 75 years or older received 20 mg of dexamethasone instead. Treatment continued in 28-day cycles until disease progression or intolerable toxicity.

“The accelerated approval of PEPAXTO in the US is an important milestone for Oncopeptides, and a major step ahead in fulfilling our mission, to bring hope to patients with difficult-to-treat hematological diseases, through innovative science,” said Marty J Duvall, Chief Executive Officer at Oncopeptides AB, in a press release. “Moving ahead, our focus is to further advance PEPAXTO. We look forward to receiving top line data from the phase 3 OCEAN-study in relapsed refractory multiple myeloma, in the second quarter. The comparative study with pomalidomide, is designed to support a future supplementary New Drug Application to expand the label.”


FDA approves Oncopeptides' PEPAXTO (melphalan flufenamide) for patients with relapsed or refractory multiple myeloma. News release. Oncopeptides AB (publ). February 26, 2021. Accessed February 26, 2021. http://cisn.co/3q2bZgq