Melphalan Flufenamide (Pepaxto)
Overview
Melphalan flufenamide is a first-in-class peptide-drug conjugate that links the alkylating agent melphalan to a dipeptide carrier. The dipeptide facilitates cellular uptake via aminopeptidases that are overexpressed in myeloma cells, where intracellular cleavage releases active melphalan. This targeted delivery aims to enhance tumor exposure while reducing systemic toxicity. The compound represents a prodrug strategy to improve the therapeutic index of cytotoxic chemotherapy.
Key Research Findings
Accelerated FDA approval was granted in February 2021 based on the single-arm HORIZON trial in relapsed/refractory multiple myeloma (ORR 29%). The confirmatory OCEAN trial subsequently showed inferior overall survival compared to standard regimens, leading to voluntary market withdrawal in October 2021. This case highlighted challenges in confirmatory trial design for accelerated approvals.
Intravenous
In Clinical Trials
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