{"entity":{"id":"pevonedistat","kind":"drug","name":"Pevonedistat","aka":["TAK-924","MLN4924"],"tldr":"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.\n\nThe 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.","status":"negative","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Pevonedistat","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pevonedistat"}],"tags":["subtype-drugs-wave"],"related":["azacitidine"],"cancers":["mds-higher-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["takeda"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/pevonedistat/","neighbours":{"drug":[{"id":"azacitidine","kind":"drug","name":"Azacitidine","route":"/drugs/azacitidine/"}],"cancer":[{"id":"mds-higher-risk","kind":"cancer","name":"Higher-risk myelodysplastic syndromes","route":"/cancers/mds-higher-risk/"}],"company":[{"id":"takeda","kind":"company","name":"Takeda","route":"/companies/takeda/"}]}}