Pepaxto (melphalan flufenamide) tested whether a peptide-drug conjugate could deliver alkylating chemotherapy more selectively into myeloma cells. It became a landmark case in accelerated approval enforcement instead.
Relying on aminopeptidase-driven cleavage inside tumor cells, it concentrated its alkylating payload where it was needed. Accelerated approval covered its use with dexamethasone for relapsed or refractory multiple myeloma after at least four prior lines of therapy.
Oncopeptides pulled it from the U.S. market in 2021, and the FDA formally withdrew approval in February 2024 after the confirmatory OCEAN trial showed worse overall survival and failed to verify clinical benefit. It is now a standard reference for contested accelerated approval withdrawals.
