Pevonedistat
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.
Overview
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.
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.
1.Pevonedistat binds its target.
Trials
topTrials recruiting now
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Latest papers
topQuery for this drug: (TITLE:"Pevonedistat" OR ABSTRACT:"Pevonedistat" OR TITLE:"TAK-924" OR ABSTRACT:"TAK-924" OR TITLE:"MLN4924" OR ABSTRACT:"MLN4924") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Pevonedistat, not a curated reading list.
Similar pages
not linked directly; found by shared links- TreatmentLenzilumab
Shares Azacitidine and the tag subtype-drugs-wave.
- Key paperAZA-001: azacitidine versus conventional care in higher-risk myelodysplastic syndromes
- TrialA Study Comparing Treatment Preference Between Oral Decitabine/Cedazuridine and Azacitidine in Myelodysplastic Syndrome, Low-Blast Acute Myeloid Leukemia, or Chronic Myelomonocytic Leukemia
- TermHypomethylating agents (azacitidine, decitabine)
- TermIPSS-R and IPSS-M (myelodysplastic syndrome risk scores)
- TreatmentDecitabine