Olutasidenib

Olutasidenib is a small-molecule inhibitor of mutated isocitrate dehydrogenase-1 (IDH1). In patients with AML, susceptible IDH1 mutations are defined as those leading to increased levels of 2-hydroxyglutarate (2-HG) in the leukemia cells and where efficacy is predicted by 1) clinically meaningful remissions with the recommended dose of olutasidenib and/or 2) inhibition of mutant IDH1 enzymatic activity at concentrations of olutasidenib sustainable at the recommended dosage according to validated methods.

• Relapsed or Refractory Acute Myeloid Leukemia REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test [see Dosage and Administration ( 2.1 ), Clinical Pharmacology ( 12.1 ), and Clinical Studies ( 14.1 )] . REZLIDHIA is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test.ICD-10: C95.90

• None. None.contraindicated

Select patients based on presence of IDH1 mutation(s). ( 2.1 ) Recommended dosage: 150 mg orally twice daily, until disease progression or unacceptable toxicity. ( 2.2 ) Take on an empty stomach at least 1 hour before or 2 hours after a meal. ( 2.2 ) 2.1 Patient Selection Select patients for the treatment of relapsed or refractory AML with REZLIDHIA based on the presence of IDH1 mutations in blood or bone marrow [see Clinical Trials ( 14.1 )] . Information on FDA- approved tests for the detection of IDH1 mutations in AML is available at http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dosage The recommended dosage of REZLIDHIA is 150 mg taken orally twice daily until disease progression or unacceptable toxicity. Administer REZLIDHIA capsules orally about the same time each day. Do not administer 2 doses within 8 hours. Take on an empty stomach at least 1 hour before or 2 hours after a meal [see Clinical Pharmacology ( 12.3 )] . For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response. Swallow REZLIDHIA capsules whole. Do not break, open, or chew the capsules. If a dose of REZLIDHIA is vomited, do not administer a replacement dose; wait until the next scheduled dose is due. If a dose of REZLIDHIA is missed or not taken at the usual time, administer the dose as soon as possible and at least 8 hours prior to the next scheduled dose. Return to the normal schedule the following day.

Hepatotoxicity : Monitor liver function tests during treatment with REZLIDHIA. If hepatotoxicity occurs, interrupt and reduce or discontinue REZLIDHIA. ( 2.3 , 5.2 ) 5.1 Differentiation Syndrome REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% (25/153) of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients [see Adverse Reactions (6.1)]. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dosage interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis. If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms.

The following clinically significant adverse reactions are described elsewhere in the labeling: Differentiation Syndrome [see Warnings and Precautions ( 5.1 )] Hepatotoxicity [see Warnings and Precautions ( 5.2 )] 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 most common (≥20%) adverse reactions, including laboratory abnormalities, are aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Rigel Pharmaceuticals, Inc. at 1-800-983-1329 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Relapsed or Refractory AML The safety of REZLIDHIA 150 mg administered twice daily was evaluated in 153 adults with relapsed or refractory AML with an IDH1 mutation [see Clinical Studies ( 14.1 )] . Among the 153 patients who received REZLIDHIA, 35% were exposed for at least 6 months and 21% were exposed for at least 1 year. The median duration of exposure to REZLIDHIA was 4.7 months (range: 0.1 to 34 months).

Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on animal embryo-fetal toxicity studies, REZLIDHIA may cause fetal harm when administered to a pregnant woman. There are no available data on REZLIDHIA use in pregnant women to evaluate for a drug-associated risk. In embryo-fetal development studies, oral olutasidenib resulted in embryo-fetal death and altered fetal growth when administered to pregnant rats and rabbits during the period of organogenesis at exposures up to 10 times and 0.7 times, respectively, the human exposure at the recommended daily 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 Olutasidenib was administered twice daily via oral gavage at dose levels of 25, 125, or 250 mg/kg/dose (50, 250, or 500 mg/kg/day) to pregnant rats during organogenesis (gestation days 6-17). An increase in fetal supernumerary rib was observed at the high dose (10 times the AUC at the clinical dose of 150 mg BID).

Metabolism

The pharmacokinetics of olutasidenib have been characterized in patients with AML following the approved recommended dosage, unless otherwise specified. The mean (%CV) olutasidenib steady-state daily area under the plasma drug concentration over time curve (AUC 0-12-h,ss ) is 43050 (34.0%) ng·h/mL and steady-state maximum plasma concentration (Cmax,ss) is 3573 (45.6%) ng/mL following the approved recommended dosage.

• Dec 1, 2022NDANDA215814Rigel Pharms

1. 1Off Label Use6927%
2. 2Death3614%
3. 3Hospitalisation3413%
4. 4Nausea2710%
5. 5Fatigue2610%
6. 6Product Dose Omission Issue249.3%
7. 7Product Prescribing Issue218.1%
8. 8Constipation166.2%
9. 9Transfusion124.6%
10. 10Pneumonia103.9%
11. 11Dyspnoea93.5%
12. 12Vomiting93.5%
13. 13Abdominal Discomfort83.1%
14. 14Product Use Issue83.1%
15. 15Asthenia72.7%

The 10 most recently updated of 20 ClinicalTrials.gov registrations naming Olutasidenib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Study of Olutasidenib and Temozolomide in HGG
  Recruiting · Phase 2 · Interventional · 60 enrolled · Rigel Pharmaceuticals
  NCT06161974updated 2026-06-12
• 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
• Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies
  Recruiting · Phase 4 · Interventional · 16 enrolled · Rigel Pharmaceuticals
  NCT07486713updated 2026-06-05
• Olutasidenib in Relapsed IDH1 Mutated AML Patients Who Have Previously Received Venetoclax
  Not yet recruiting · Phase 2 · Interventional · 25 enrolled · Timothy Pardee
  NCT07471841updated 2026-06-01
• A Clinical Trial of Olutasidenib in Patients With Acute Myeloid Leukemia
  Recruiting · Phase 2 · Interventional · 3 enrolled · Kissei Pharmaceutical Co., Ltd.
  NCT07604064updated 2026-05-27
• Phase 1b/2 Study of Decitabine and Venetoclax in Combination With the Targeted Mutant IDH1 Inhibitor Olutasidenib
  Recruiting · Phase 1 · Phase 2 · Interventional · 78 enrolled · M.D. Anderson Cancer Center
  NCT06445959updated 2026-05-20
• A Phase 2 Study Evaluating Olutasidenib in Combination With Hypomethylating Agents in Patients With IDH1-mutated Higher-risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Advanced Myeloproliferative Neoplasm
  Withdrawn · Phase 2 · Interventional · 0 enrolled · M.D. Anderson Cancer Center
  NCT06597734updated 2026-05-20
• Phase 1/1b Trial Of Olutasidenib And Ziftomenib For NPM1 And IDH1 Co-Mutated Acute Myeloid Leukemia
  Not yet recruiting · Phase 1 · Interventional · 20 enrolled · M.D. Anderson Cancer Center
  NCT07411586updated 2026-05-15
• Testing the Use of an IDH1 Inhibitor, Olutasidenib, in Acute Myeloid Leukemia Added to ASTX727 and Venetoclax; in High-Risk MDS Added to ASTX727; and Alone in Low Risk MDS (A MyeloMATCH Treatment Substudy)
  Not yet recruiting · Phase 2 · Interventional · 132 enrolled · National Cancer Institute (NCI)
  NCT07153497updated 2026-05-13
• Olutasidenib, Venetoclax, and Azacitidine in IDH1 Mutated Newly Diagnosed Acute Myeloid Leukemia Patients Eligible for Intensive Induction Chemotherapy
  Recruiting · Phase 2 · Interventional · 16 enrolled · Justin Watts, MD
  NCT06782542updated 2026-04-16

Frequently asked questions

How does Olutasidenib work?

Olutasidenib is a small-molecule inhibitor of mutated isocitrate dehydrogenase-1 (IDH1). In patients with AML, susceptible IDH1 mutations are defined as those leading to increased levels of 2-hydroxyglutarate (2-HG) in the leukemia cells and where efficacy is predicted by 1) clinically meaningful remissions with the recommended dose of olutasidenib and/or 2) inhibition of mutant IDH1 enzymatic activity at concentrations of olutasidenib sustainable at the recommended dosage according to validated methods.

What is Olutasidenib used for?

According to FDA labeling, Olutasidenib carries indications including: Relapsed or Refractory Acute Myeloid Leukemia REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test [see Dosage and Administration ( 2.1 ), Clinical Pharmacology ( 12.1 ), and Clinical Studies ( 14.1 )] . REZLIDHIA is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 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 Olutasidenib?

Olutasidenib is classified as Isocitrate dehydrogenase (IDH) inhibitors, Isocitrate Dehydrogenase 1 Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Olutasidenib?

Olutasidenib is marketed under brand names including Rezlidhia.

What are the contraindications for Olutasidenib?

Olutasidenib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.