# Melphalan flufenamide

Source: https://onco.cc/drugs/melflufen/  
OnCo record `melflufen` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A myeloma drug given accelerated approval in 2021 and withdrawn in the US months later when its confirmatory trial suggested it shortened survival.

## Summary

Melflufen is a lipophilic peptide-conjugated alkylator activated by aminopeptidases enriched in myeloma cells. Accelerated approval (February 2021) rested on the single-arm HORIZON response rate. The confirmatory OCEAN trial met its PFS endpoint but showed an overall survival detriment in a subgroup (patients with prior autologous transplant), leading to a partial clinical hold, an ODAC vote against, and US withdrawal (2021; formal FDA withdrawal 2024). It remains approved in the EU with restrictions.

Lesson: accelerated approval on response rate carries real risk when the confirmatory trial shows harm; the same subgroup could be a true signal or noise, and regulators in the US and EU read it differently.

## Fields

- Kind: Treatment
- Status: withdrawn
- Last checked: 2026-09-06
- Tags: failure; lesson:regulatory
- Brand: Pepaxto
- Code: melflufen
- Modality: Peptide-drug conjugate
- Mechanism: Peptidase-activated alkylating prodrug of melphalan.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Melphalan_flufenamide
- FDA withdrawal of Pepaxto approval (Feb 2024) (page moved; nearest live section): https://www.fda.gov/drugs/drug-safety-and-availability/

## Connected records

- cancers: [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/)
- technologies: [Peptide-drug & small-molecule-drug conjugates](https://onco.cc/technologies/peptide-drug-conjugate/)
- companies: [Oncopeptides](https://onco.cc/companies/oncopeptides/)
- terms: [Accelerated approval](https://onco.cc/terms/accelerated-approval/)
- trials: [A Study of Melphalan Flufenamide (Melflufen) Plus Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma](https://onco.cc/trials/nct02963493/), [A Study of Melphalan Flufenamide (Melflufen)-Dex or Pomalidomide-dex for RRMM Patients Refractory to Lenalidomide](https://onco.cc/trials/nct03151811/), [Study of Melflufen (Melphalan Flufenamide) in Combination With Daratumumab in Relapsed-Refractory Multiple Myeloma](https://onco.cc/trials/nct04649060/)
- bottlenecks: [Failures are hidden](https://onco.cc/bottlenecks/b-negative-results/)

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