# Pevonedistat

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

## TL;DR

Pevonedistat was a first-in-class drug that jammed part of the cell's protein-disposal system. Promising with azacitidine in a mid-stage trial for higher-risk myelodysplastic syndromes, it failed to beat azacitidine alone in the phase 3 PANTHER trial in 2021.

## Summary

Pevonedistat (TAK-924, MLN4924) was Takeda's inhibitor of the NEDD8-activating enzyme, the first drug in its class to reach late-stage trials. In the randomised phase 2 Pevonedistat-2001 study, adding it to azacitidine lengthened event-free survival and improved responses in higher-risk myelodysplastic syndromes, which prompted a phase 3 programme.

The phase 3 PANTHER trial in higher-risk myelodysplastic syndromes, chronic myelomonocytic leukaemia and low-blast acute myeloid leukaemia did not meet its primary endpoint of event-free survival when it reported in 2021, and Takeda ended development in these diseases. The higher-risk MDS page lists it with sabatolimab, magrolimab and eprenetapopt among the azacitidine partners that failed.

## Fields

- Kind: Treatment
- Status: negative
- Last checked: 2026-09-17
- Also known as: TAK-924; MLN4924
- Tags: subtype-drugs-wave
- Code: TAK-924
- Modality: Intravenous NEDD8-activating enzyme (NAE) inhibitor
- Mechanism: Blocks the NEDD8-activating enzyme, which switches on cullin-RING ubiquitin ligases; without neddylation, proteins these ligases normally degrade accumulate, causing DNA re-replication and cell death in myeloid blasts.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Pevonedistat
- Wikipedia: https://en.wikipedia.org/wiki/Pevonedistat

## Connected records

- drugs: [Azacitidine](https://onco.cc/drugs/azacitidine/)
- cancers: [Higher-risk myelodysplastic syndromes](https://onco.cc/cancers/mds-higher-risk/)
- companies: [Takeda](https://onco.cc/companies/takeda/)

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JSON: https://onco.cc/api/v1/entities/pevonedistat.json