Vorasidenib

Vorasidenib is a small molecule inhibitor that targets isocitrate dehydrogenase-1 and 2 (IDH1 and IDH2) enzymes. In vitro, vorasidenib inhibited the IDH1 wild type and mutant variants, including R132H and the IDH2 wild type and mutant variants.

• VORANIGO is indicated for the treatment of adult and pediatric patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 (IDH1) or isocitrate dehydrogenase-2 (IDH2) mutation, as detected by an FDA-approved test, following surgery including biopsy, sub-total resection, or gross total resection [see Dosage and Administration (2.1) , Clinical Pharmacology (12.1) and Clinical Studies (14) ] . VORANIGO is an isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) inhibitor indicated for the treatment of adult and pediatric patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation, as detected by an FDA-approved test, following surgery including biopsy, sub-total resection, or gross total resection.

• None. None.contraindicated

Recommended dosage in adults: ( 2.3 ) 40 mg orally once daily Recommended dosage in pediatric patients 12 years of age and older based on body weight: ( 2.3 ) ≥40 kg : 40 mg orally once daily <40 kg : 20 mg orally once daily Take with or without food. ( 2.3 ) 2.1 Recommended Evaluation Before Initiating VORANIGO Before initiating VORANIGO, evaluate blood chemistry and liver laboratory tests [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ]. 2.2 Patient Selection Select patients with Grade 2 astrocytoma or oligodendroglioma for treatment with VORANIGO based on the presence of IDH1 or IDH2 mutations in tumor specimens [see Clinical Studies (14) ] . Information on FDA-approved tests for detection of IDH1 or IDH2 mutations in Grade 2 astrocytoma or oligodendroglioma for selecting patients for treatment with VORANIGO is available at: https://www.fda.gov/CompanionDiagnostics. 2.3 Recommended Dosage and Administration Recommended Dosage Adult Patients The recommended dosage of VORANIGO in adult patients is 40 mg orally once daily until disease progression or unacceptable toxicity. Pediatric Patients 12 Years and Older The recommended dosage of VORANIGO in pediatric patients 12 years and older is based on body weight: Patients weighing ≥40 kg: 40 mg orally once daily Patients weighing <40 kg: 20 mg orally once daily Continue treatment with VORANIGO until disease progression or unacceptable toxicity. Administration Swallow VORANIGO tablets whole with water with or without food [see Clinical Pharmacology (12.3) ] . Do not split, crush or chew tablets.

Hepatotoxicity : Monitor liver function tests every 2 weeks during the first 2 months of treatment, then monthly for the first 2 years of treatment, and as clinically indicated. Withhold, reduce the dose or discontinue VORANIGO based on severity. ( 2.3 , 5.1 ) Embryo-Fetal Toxicity : VORANIGO can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective nonhormonal contraception. ( 5.2 , 8.1 , 8.3 ) 5.1 Hepatotoxicity VORANIGO can cause hepatic transaminase elevations, which can lead to hepatic failure, hepatic necrosis, and autoimmune hepatitis. In the pooled safety population [see Adverse Reactions (6.1) ] , 58% of patients treated with VORANIGO experienced increased ALT and 44% of patients experienced increased AST. Grade 3 or 4 increased ALT or AST occurred in 9% and 4.8% of patients respectively. Among these patients, 4.1% (10/244) had concurrent Grade 3 to 4 ALT or AST elevations. A total of 34% of patients treated with VORANIGO had increased gamma-glutamyl transferase (GGT), of these 2.2% were Grade 3 or 4. Bilirubin increases occurred in 4.8% of patients treated with VORANIGO, with 0.4% Grade 3 or 4. Nine percent of patients treated with VORANIGO had increased alkaline phosphatase, with 0.9% Grade 3 or 4. Two patients met the laboratory criteria for Hy's Law and had concurrent elevations in ALT or AST >3 times the upper limit of normal and total bilirubin >2 times the upper limit of normal; these events were associated with cases of autoimmune hepatitis and hepatic failure.

The following clinically significant adverse reactions are described elsewhere in the labeling: Hepatotoxicity [see Warnings and Precautions (5.1) ] The most common (≥15%) adverse reactions include fatigue, headache, COVID-19, musculoskeletal pain, diarrhea, nausea, and seizure. Grade 3 or 4 (≥2%) laboratory abnormalities were ALT increased, AST increased, GGT increased, and neutrophils decreased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Servier Pharmaceuticals at 1-800-807-6124 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. Adverse reactions described in the WARNINGS AND PRECAUTIONS reflect exposure to VORANIGO 40 mg orally once daily until disease progression or unacceptable toxicity in the 244 patients with astrocytoma or oligodendroglioma with susceptible IDH1 or IDH2 mutation in trials AG881-C-002 (NCT02481154, n=11), AG120-881-001 (NCT03343197, n=14) and INDIGO (NCT04164901, n=167 randomized patients and n=52 crossover patients). Among the 244 patients who received VORANIGO, 78% were exposed for 6 months or longer and 44% were exposed for greater than one year. In this pooled safety population, the most common (≥15%) adverse reactions were fatigue (33%), headache (28%), COVID-19 (28%), musculoskeletal pain (24%), diarrhea (21%), nausea (20%), and seizure (16%).

Lactation : Advise not to breastfeed. ( 8.2 ) Infertility : May impair fertility in males and females. ( 8.3 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , VORANIGO can cause fetal harm when administered to a pregnant woman. There are no available data on VORANIGO use in pregnant women to inform a drug-associated risk. In animal embryo-fetal development studies, oral administration of vorasidenib to pregnant rats and rabbits during the period of organogenesis caused embryo-fetal toxicity at ≥8 times the human exposure based on the AUC at the highest recommended dose (see Data ) . Advise pregnant women of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study, vorasidenib was administered to pregnant rats via oral gavage at dose levels of 10, 25, and 75 mg/kg/day during the period of organogenesis (gestation days 6 to 17). Embryo-fetal toxicity (higher incidence of early resorptions, and visceral malformations of kidney and testes) occurred in rats at the maternally toxic dose of 75 mg/kg/day (approximately 170 times the human exposure based on the AUC at the highest recommended dose).

Metabolism

Vorasidenib maximum plasma concentration (C max ) and AUC increased approximately proportionally over the dose range of 10 to 200 mg (0.2 to 4 times the exposure of the highest approved recommended dosage) following once daily administration of single and multiple doses. At the highest approved recommended dosage, steady state mean (CV%) C max is 133 ng/mL (73%) and AUC is 1,988 h•ng/mL (95%).

• Aug 6, 2024NDANDA218784Servier

1. 1Alanine Aminotransferase Increased6314%
2. 2Aspartate Aminotransferase Increased5112%
3. 3Fatigue4510%
4. 4Malignant Neoplasm Progression347.8%
5. 5Headache337.6%
6. 6Hepatic Cytolysis337.6%
7. 7Seizure296.6%
8. 8Nausea276.2%
9. 9Hepatic Enzyme Increased265.9%
10. 10Gamma-glutamyltransferase Increased245.5%
11. 11Hepatotoxicity153.4%
12. 12Diarrhoea143.2%
13. 13Drug-induced Liver Injury143.2%
14. 14Fall122.7%
15. 15Blood Bilirubin Increased112.5%

The 10 most recently updated of 21 ClinicalTrials.gov registrations naming Vorasidenib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Pharmacokinetic Study of Vorasidenib in Severe Hepatically Impaired and Matched-Control Participants
  Recruiting · Phase 1 · Interventional · 20 enrolled · Institut de Recherches Internationales Servier (I.R.I.S.)
  NCT07250633updated 2026-06-05
• VorAsidenib With Lomustine In Patients With rEcurrent IDH-mutaNT Glioma Harboring IDH1 and/or IDH2 Mutations
  Not yet recruiting · Phase 1 · Interventional · 24 enrolled · Megan Mantica
  NCT07629089updated 2026-06-05
• Vorasidenib in Combination With Temozolomide (TMZ) in IDH-mutant Glioma
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 51 enrolled · Institut de Recherches Internationales Servier
  NCT06478212updated 2026-06-04
• Phase 3 Study of Vorasidenib (S095032/AG-881) in Asian Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 orIDH2 Mutation
  Active not recruiting · Phase 3 · Interventional · 57 enrolled · Servier
  NCT06780930updated 2026-06-04
• Vorasidenib Maintenance for IDH Mutant Astrocytoma
  Recruiting · Phase 3 · Interventional · 468 enrolled · European Organisation for Research and Treatment of Cancer - EORTC
  NCT06809322updated 2026-05-22
• A Drug-drug Interaction Study of Vorasidenib and a Combined Oral Contraceptive in Healthy Female Participants
  Completed · Phase 1 · Interventional · 28 enrolled · Institut de Recherches Internationales Servier (I.R.I.S.)
  NCT07235774updated 2026-05-12
• Patient Voice in the Treatment of Low-grade Gliomas: Use of Patient-reported Outcomes, Vorasidenib and Radiotherapy Compared
  Recruiting · Observational · 90 enrolled · Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
  NCT07547163updated 2026-04-23
• Vorasidenib Guided by AGX PET in Recurrent/Low-grade Glioma
  Not yet recruiting · Interventional · 10 enrolled · Huashan Hospital
  NCT07469735updated 2026-03-13
• Study of Vorasidenib and Pembrolizumab Combination in Recurrent or Progressive IDH-1 Mutant Glioma
  Active not recruiting · Phase 1 · Interventional · 60 enrolled · Institut de Recherches Internationales Servier
  NCT05484622updated 2026-03-12
• Drug-drug Interaction Study of Vorasidenib With Bupropion, Repaglinide, Flurbiprofen, Omeprazole, Midazolam, and Rosuvastatin in Healthy Adult Participants
  Completed · Phase 1 · Interventional · 28 enrolled · Institut de Recherches Internationales Servier (I.R.I.S.)
  NCT07235748updated 2026-02-17

Frequently asked questions

How does Vorasidenib work?

Vorasidenib is a small molecule inhibitor that targets isocitrate dehydrogenase-1 and 2 (IDH1 and IDH2) enzymes. In vitro, vorasidenib inhibited the IDH1 wild type and mutant variants, including R132H and the IDH2 wild type and mutant variants.

What is Vorasidenib used for?

According to FDA labeling, Vorasidenib carries indications including: VORANIGO is indicated for the treatment of adult and pediatric patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 (IDH1) or isocitrate dehydrogenase-2 (IDH2) mutation, as detected by an FDA-approved test, following surgery including biopsy, sub-total resection, or gross total resection [see Dosage and Administration (2.1) , Clinical Pharmacology (12.1) and Clinical Studies (14) ] . VORANIGO is an isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) inhibitor indicated for the treatment of adult and pediatric patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation, as detected by an FDA-approved test, following surgery including biopsy, sub-total resection, or gross total resection.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Vorasidenib?

Vorasidenib is classified as Isocitrate dehydrogenase (IDH) inhibitors, Isocitrate Dehydrogenase 1 Inhibitor, Isocitrate Dehydrogenase 2 Inhibitor, Cytochrome P450 3A Inducers, Isocitrate Dehydrogenase 1 Inhibitors, Isocitrate Dehydrogenase 2 Inhibitors.

What are the brand names for Vorasidenib?

Vorasidenib is marketed under brand names including Voranigo.

What are the contraindications for Vorasidenib?

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