{"entity":{"id":"enasidenib","kind":"drug","name":"Enasidenib","aka":[],"tldr":"Enasidenib is the IDH2 counterpart of ivosidenib, approved in the US for relapsed disease but never approved in Europe after it failed to extend survival in a confirmatory trial.","summary":"Approved 2017 (US) for relapsed/refractory IDH2-mutated AML on a single-arm study (CR+CRh ~23%). The phase 3 IDHENTIFY trial did not improve OS versus conventional care; the EMA application was withdrawn (2019), and BMS later announced market withdrawal in some territories while maintaining US availability. Illustrates the gap between response rate and survival endpoints in relapsed AML.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Enasidenib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Enasidenib"}],"tags":["confirmatory-trial-negative"],"related":["idh2-mutation"],"cancers":["aml","aml-idh","sinonasal-undifferentiated-carcinoma"],"sections":[],"technologies":["epigenetic-drugs","idh-inhibitors"],"targets":["idh"],"drugs":[],"companies":["bms"],"institutions":[],"pathways":[],"terms":["differentiation-syndrome"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Idhifa","modality":"Small-molecule IDH2 inhibitor","mechanism":"Allosteric inhibitor of mutant IDH2 (R140Q and R172K), lowering 2-HG and inducing differentiation.","approvals":[{"region":"US","year":2017,"indication":"Relapsed/refractory IDH2-mutated AML"}],"mechanismSteps":["Mutant IDH2 produces 2-HG in mitochondria","Enasidenib binds the mutant dimer and blocks 2-HG","Differentiation block lifts; blasts mature over weeks","Response is often gradual, without marrow aplasia"],"dosing":{"route":"Oral","schedule":"100 mg once daily until progression (minimum 6 months)","monitoring":"Differentiation syndrome (boxed warning), bilirubin (indirect hyperbilirubinaemia from UGT1A1 inhibition)","source":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Idhifa"},"toxicity":[{"event":"Differentiation syndrome","anyGradePct":14,"source":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Idhifa"},{"event":"Indirect hyperbilirubinaemia","anyGradePct":81},{"event":"Nausea","anyGradePct":50}],"access":[],"regulatoryEvents":[{"date":"2017-08-01","type":"approval","region":"US","note":"Single-arm AG221-C-001"},{"date":"2019-12-01","type":"withdrawal","region":"EU","note":"Marketing application withdrawn after EMA objections on efficacy","source":"https://www.ema.europa.eu/en/documents/medicine-qa/questions-and-answers-withdrawal-application-marketing-authorisation-idhifa-enasidenib_en.pdf"}]},"route":"/drugs/enasidenib/","neighbours":{"biomarker":[{"id":"idh2-mutation","kind":"biomarker","name":"IDH2 mutation (R140 and R172)","route":"/biomarkers/idh2-mutation/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-idh","kind":"cancer","name":"IDH1- and IDH2-mutated acute myeloid leukaemia","route":"/cancers/aml-idh/"},{"id":"sinonasal","kind":"cancer","name":"Nasal cavity and paranasal sinus cancers (including esthesioneuroblastoma)","route":"/cancers/sinonasal/"},{"id":"sinonasal-undifferentiated-carcinoma","kind":"cancer","name":"Sinonasal undifferentiated carcinoma (SNUC) and SWI/SNF-deficient sinonasal carcinoma","route":"/cancers/sinonasal-undifferentiated-carcinoma/"}],"technology":[{"id":"epigenetic-drugs","kind":"technology","name":"Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)","route":"/technologies/epigenetic-drugs/"},{"id":"idh-inhibitors","kind":"technology","name":"IDH inhibitors","route":"/technologies/idh-inhibitors/"}],"target":[{"id":"idh","kind":"target","name":"IDH1 / IDH2","route":"/targets/idh/"}],"company":[{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"}],"term":[{"id":"differentiation-syndrome","kind":"term","name":"Differentiation syndrome","route":"/terms/differentiation-syndrome/"}],"pathway":[{"id":"idh-2hg","kind":"pathway","name":"Mutant IDH / 2-hydroxyglutarate","route":"/pathways/idh-2hg/"}],"paper":[{"id":"paper-enasidenib-idh2-stein-blood-2017","kind":"paper","name":"Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukaemia","route":"/key-papers/paper-enasidenib-idh2-stein-blood-2017/"},{"id":"paper-jo-idh2-r172-mutations-snuc-mod-pathol-2017","kind":"paper","name":"Recurrent IDH2 R172X mutations in sinonasal undifferentiated carcinoma","route":"/key-papers/paper-jo-idh2-r172-mutations-snuc-mod-pathol-2017/"}],"roadmap":[{"id":"epigenetics-roadmap","kind":"roadmap","name":"Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome","route":"/roadmaps/epigenetics-roadmap/"}],"trial":[{"id":"beat-aml-master-trial","kind":"trial","name":"Beat AML Master Trial","route":"/trials/beat-aml-master-trial/"}]}}