Enasidenib

Enasidenib is a small molecule inhibitor of the isocitrate dehydrogenase 2 (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.

• IDHIFA is an isocitrate dehydrogenase-2 inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test ( 1.1 ). 1.1 Acute Myeloid Leukemia IDHIFA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test.ICD-10: C95.90

• None. None ( 4 ).contraindicated

100 mg orally once daily until disease progression or unacceptable toxicity ( 2.2 ). 2.1 Patient Selection Select patients for the treatment of AML with IDHIFA based on the presence of IDH2 mutations in the blood or bone marrow [see Indications and Usage (1.1) and Clinical Studies (14.1) ] . Information on FDA-approved tests for the detection of IDH2 mutations in AML is available at http://www.fda.gov/CompanionDiagnostics . 2.2 Recommended Dosage The recommended dosage of IDHIFA is 100 mg taken orally once daily with or without food until disease progression or unacceptable toxicity. For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response. Swallow tablets whole. Do not chew, split, or crush IDHIFA tablets. Administer IDHIFA tablets orally about the same time each day. If a dose of IDHIFA is vomited, missed, or not taken at the usual time, administer the dose as soon as possible on the same day, and return to the normal schedule the following day. 2.3 Monitoring and Dosage Modifications for Toxicities Assess blood counts and blood chemistries for leukocytosis and tumor lysis syndrome prior to the initiation of IDHIFA and monitor at a minimum of every 2 weeks for at least the first 3 months during treatment. Manage any abnormalities promptly [see Adverse Reactions (6.1) ] . Interrupt dosing or reduce dose for toxicities. See Table 1 for dosage modification guidelines.

Embryo-Fetal Toxicity : IDHIFA can cause fetal harm. Advise patients of the potential risk to a fetus and use effective contraception ( 5.2 , 8.1 , 8.3 ). 5.1 Differentiation Syndrome In the clinical trial, 14% of patients treated with IDHIFA experienced differentiation syndrome, which may be life-threatening or fatal if not treated. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells. While there is no diagnostic test for differentiation syndrome, symptoms in patients treated with IDHIFA included acute respiratory distress represented by dyspnea and/or hypoxia (68%) and need for supplemental oxygen (76%); pulmonary infiltrates (73%) and pleural effusion (45%); renal impairment (70%); fever (36%); lymphadenopathy (33%); bone pain (27%); peripheral edema with rapid weight gain (21%); and pericardial effusion (18%). Hepatic, renal, and multi-organ dysfunction have also been observed. Differentiation syndrome has been observed with and without concomitant hyperleukocytosis, in as early as 1 day and up to 5 months after IDHIFA initiation. If differentiation syndrome is suspected, initiate oral or intravenous corticosteroids (e.g., dexamethasone 10 mg every 12 hours) and hemodynamic monitoring until improvement. Taper corticosteroids only after resolution of symptoms. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid treatment.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Differentiation Syndrome [see Warnings and Precautions (5.1) ] The most common adverse reactions (≥20%) are nausea, vomiting, diarrhea, elevated bilirubin, and decreased appetite ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Bristol Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety evaluation of single-agent IDHIFA is based on 214 patients with relapsed or refractory AML who were assigned to receive 100 mg daily [see Clinical Studies (14.1) ] . The median duration of exposure to IDHIFA was 4.3 months (range 0.3 to 23.6). The 30-day and 60-day mortality rates observed with IDHIFA were 4.2% (9/214) and 11.7% (25/214), respectively. Serious adverse reactions were reported in 77.1% of patients. The most frequent serious adverse reactions (≥2%) were leukocytosis (10%), diarrhea (6%), nausea (5%), vomiting (3%), decreased appetite (3%), tumor lysis syndrome (5%), and differentiation syndrome (8%). Differentiation syndrome events characterized as serious included pyrexia, renal failure acute, hypoxia, respiratory failure, and multi-organ failure.

Lactation : Advise not to breastfeed ( 8.2 ). 8.1 Pregnancy Risk Summary Based on animal embryo-fetal toxicity studies, IDHIFA can cause fetal harm when administered to a pregnant woman. There are no available data on IDHIFA use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal embryo-fetal toxicity studies, oral administration of enasidenib to pregnant rats and rabbits during organogenesis was associated with embryo-fetal mortality and alterations to growth starting at 0.1 times the steady state clinical exposure based on the AUC at the recommended human dose (see Data). Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Data Animal Data Enasidenib administered to pregnant rats at a dose of 30 mg/kg twice daily during organogenesis (gestation days 6-17) was associated with maternal toxicity and adverse embryo-fetal effects including post-implantation loss, resorptions, decreased viable fetuses, lower fetal birth weights, and skeletal variations. These effects occurred in rats at approximately 1.6 times the clinical exposure at the recommended human daily dose of 100 mg/day.

Metabolism

The peak plasma concentration (C max ) is 1.4 mcg/mL [coefficient of variation (CV%) 50%] after a single dose of 100 mg, and 13.1 mcg/mL (CV% 45%) at steady state for 100 mg daily. The area under concentration time curve (AUC) of enasidenib increases in an approximately dose proportional manner from 50 mg (0.5 times approved recommended dosage) to 450 mg (4.5 times approved recommended dosage) daily dose.

• Aug 1, 2017NDANDA209606Bristol Myers Squibb

1. 1Death66020%
2. 2Off Label Use2297.1%
3. 3Fatigue2126.5%
4. 4Nausea1915.9%
5. 5Hospitalisation1685.2%
6. 6Diarrhoea1404.3%
7. 7Platelet Count Decreased1223.8%
8. 8Acute Myeloid Leukaemia1193.7%
9. 9Decreased Appetite1163.6%
10. 10Drug Ineffective1013.1%
11. 11Asthenia882.7%
12. 12Full Blood Count Decreased802.5%
13. 13Pyrexia722.2%
14. 14White Blood Cell Count Decreased722.2%
15. 15Pneumonia672.1%

The 10 most recently updated of 49 ClinicalTrials.gov registrations naming Enasidenib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• 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)
  Recruiting · Phase 2 · Interventional · 54 enrolled · National Cancer Institute (NCI)
  NCT06577441updated 2026-06-11
• MYELOMATCH: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study or Standard of Care Treatment Within myeloMATCH (MyeloMATCH Screening Trial)
  Recruiting · Phase 2 · Interventional · 2,000 enrolled · National Cancer Institute (NCI)
  NCT05564390updated 2026-06-11
• Comparing New Treatments for People With Newly Diagnosed Acute Myeloid Leukemia That Has an IDH2 Gene Change (A MyeloMATCH Treatment Trial)
  Recruiting · Phase 2 · Interventional · 93 enrolled · National Cancer Institute (NCI)
  NCT06672146updated 2026-06-11
• IDH Targeted/Non- Targeted vs Non-targeted/IDH-targeted Approaches in the Treatment of Newly Diagnosed IDH Mutated AML Patients Not Candidates for Intensive Induction Therapy (I- DATA Study)
  Recruiting · Phase 2 · Interventional · 125 enrolled · Alice Mims
  NCT05401097updated 2026-06-08
• Enasidenib in IDH2-Mutated Malignant Sinonasal and Skull Base Tumors
  Recruiting · Phase 2 · Interventional · 40 enrolled · National Cancer Institute (NCI)
  NCT06176989updated 2026-06-03
• Enasidenib for Patients With Clonal Cytopenia of Undetermined Significance and Mutations in IDH2A Decentralized Trial
  Recruiting · Phase 2 · Interventional · 15 enrolled · Washington University School of Medicine
  NCT06240754updated 2026-05-27
• Safety Study of AG-120 or AG-221 in Combination With Induction and Consolidation Therapy in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) With an IDH1 and/or IDH2 Mutation
  Active not recruiting · Phase 1 · Interventional · 153 enrolled · Institut de Recherches Internationales Servier
  NCT02632708updated 2026-05-22
• Decitabine/Cedazuridine and Venetoclax in Combination With Ivosidenib or Enasidenib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
  Recruiting · Phase 1 · Phase 2 · Interventional · 84 enrolled · M.D. Anderson Cancer Center
  NCT04774393updated 2026-05-20
• Enasidenib (AG-221) Maintenance Post Allogeneic HCT in Patients With IDH2 Mutation
  Recruiting · Phase 2 · Interventional · 35 enrolled · City of Hope Medical Center
  NCT03728335updated 2026-05-20
• Enasidenib in Combination With Cobimetinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
  Completed · Phase 1 · Interventional · 3 enrolled · City of Hope Medical Center
  NCT05441514updated 2026-05-05

Frequently asked questions

How does Enasidenib work?

Enasidenib is a small molecule inhibitor of the isocitrate dehydrogenase 2 (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.

What is Enasidenib used for?

According to FDA labeling, Enasidenib carries indications including: IDHIFA is an isocitrate dehydrogenase-2 inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test ( 1.1 ). 1.1 Acute Myeloid Leukemia IDHIFA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Enasidenib?

Enasidenib is classified as Isocitrate dehydrogenase (IDH) inhibitors, Isocitrate Dehydrogenase 2 Inhibitor, Isocitrate Dehydrogenase 2 Inhibitors, Increased Myeloid Cell Production.

What are the brand names for Enasidenib?

Enasidenib is marketed under brand names including Idhifa.

What are the contraindications for Enasidenib?

Enasidenib labeling lists contraindications including: None. None ( 4 ).. Always consult the full prescribing information and a clinician.