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Idhifa (ENASIDENIB)
Idhifa works by blocking the IDH2 enzyme, which is mutated in some AML cells, to prevent the production of a toxic metabolite that promotes cancer growth.
Idhifa (enasidenib) is a small molecule inhibitor of isocitrate dehydrogenase 2 (IDH2), a mitochondrial enzyme. It was originally developed by Celgene Corp and is now owned by Bristol Myers Squibb. Idhifa is FDA-approved for the treatment of acute myeloid leukemia (AML) with a specific IDH2 mutation. The drug has a half-life of 7.9 days and is not yet off-patent. Key safety considerations include the risk of differentiation syndrome and IDH differentiation syndrome.
At a glance
| Generic name | ENASIDENIB |
|---|---|
| Sponsor | Bristol-Myers Squibb |
| Drug class | Isocitrate Dehydrogenase 2 Inhibitor |
| Target | Isocitrate dehydrogenase [NADP], mitochondrial |
| Modality | Small molecule |
| Therapeutic area | Oncology |
| Phase | FDA-approved |
| First approval | 2017 |
Mechanism of action
Enasidenib is small molecule inhibitor of the isocitrate dehydrogenase (IDH2) enzyme. Enasidenib targets the mutant IDH2 variants R140Q, R172S, and R172K at approximately 40-fold lower concentrations than the wild-type enzyme in vitro. Inhibition of the mutant IDH2 enzyme by enasidenib led to decreased 2-hydroxyglutarate (2-HG) levels and induced myeloid differentiation in vitro and in vivo in mouse xenograft models of IDH2 mutated AML. In blood samples from patients with AML with mutated IDH2, enasidenib decreased 2-HG levels, reduced blast counts and increased percentages of mature myeloid cells.
Approved indications
- Acute myeloid leukemia, disease
Boxed warnings
- WARNING: DIFFERENTIATION SYNDROME Patients treated with IDHIFA have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, lymphadenopathy, bone pain, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ] . WARNING: DIFFERENTIATION SYNDROME See full prescribing information for complete boxed warning. Patients treated with IDHIFA have experienced symptoms of differentiation syndrome, which can be fatal if not treated. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution ( 5.1 , 6.1 ).
Common side effects
- Nausea
- Diarrhea
- Vomiting
- Decreased appetite
- Leukocytosis
- Differentiation syndrome
- Tumor lysis syndrome
- Elevated bilirubin
- Pyrexia
- Renal failure acute
- Hypoxia
- Respiratory failure
Key clinical trials
- MYELOMATCH: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study or Standard of Care Treatment Within myeloMATCH (MyeloMATCH Screening Trial) (PHASE2)
- Comparing New Treatments for People With Newly Diagnosed Acute Myeloid Leukemia That Has an IDH2 Gene Change (A MyeloMATCH Treatment Trial) (PHASE2)
- Testing the Addition of an IDH2 Inhibitor, Enasidenib, to Usual Treatment (Cedazuridine-Decitabine) for Higher-Risk Myelodysplastic Syndrome (MDS) With IDH2 Mutation (A MyeloMATCH Treatment Trial) (PHASE2)
- A Study of Gilteritinib in Combination With Ivosidenib or Enasidenib in People With Acute Myeloid Leukemia (AML) (PHASE1)
- Enasidenib (AG-221) Maintenance Post Allogeneic HCT in Patients With IDH2 Mutation (PHASE2)
- Enasidenib and Azacitidine in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia and IDH2 Gene Mutation (PHASE2)
- A Study to Assess the Safety and Efficacy of Two Combinations of Isocitrate Dehydrogenase (IDH) Mutant Targeted Therapies Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) Harboring IDH Mutations Who Are Not Candidates to Receive Intensive Induction Chemotherapy (PHASE1,PHASE2)
- Azacitidine and Enasidenib in Treating Patients With IDH2-Mutant Myelodysplastic Syndrome (PHASE2)
Patents
| Patent | Expiry | Type |
|---|---|---|
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| FDA label | Mechanism, indications, dosing, boxed warnings, drug interactions |
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
| FDA Orange Book | Patents + exclusivity |
Competitive intelligence
For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:
- Idhifa CI brief — competitive landscape report
- Idhifa updates RSS · CI watch RSS
- Bristol-Myers Squibb portfolio CI