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INDIGO trial: Safety of VORANIGO® vs placebo in 330 patients with mIDH glioma¹

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Most common ARs Duration of exposure Adverse reactions Laboratory abnormalities

The safety results shown are based on the primary analysis.¹ The safety profile of VORANIGO for the extended analysis was consistent with the primary analysis.²

The INDIGO trial assessed adverse reactions (ARs) of VORANIGO compared with placebo¹

ARs reported in ≥5% of patients in the INDIGO trial¹

VORANIGO 40 mg daily (n=167)

Placebo (n=163)

Adverse reaction^a	All Grades (%)	Grades 3 or 4 (%)
General disorders		VORANIGO 40 mg daily (n=167) Placebo (n=163)
Fatigue^b	37 37% 36 36%	0.6 0.6% 1.2 1.2%
Infections and infestations
COVID-19	33 33% 29 29%	0 0% 0 0%
Nervous system disorders
Seizure^c	16 16% 15 15%	4.2 4.2% 3.7 3.7%
Musculoskeletal and connective tissue disorders
Musculoskeletal pain^d	26 26% 25 25%	0 0% 1.8 1.8%
Gastrointestinal disorders
Diarrhea^e	25 25% 17 17%	0.6 0.6% 0.6 0.6%
Constipation	13 13% 12 12%	0 0% 0 0%
Abdominal pain^f	13 13% 12 12%	0 0% 0 0%
Decreased appetite	9 9% 3.7 3.7%	0 0% 0 0%

^aARs are based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

^bGrouped term includes asthenia.

^cGrouped term includes partial seizures, generalized tonic-clonic seizure, epilepsy, clonic convulsion, and simple partial seizures.

^dGrouped term includes arthralgia, back pain, non-cardiac chest pain, pain in extremity, myalgia, neck pain, musculoskeletal chest pain, arthritis, and musculoskeletal stiffness.

^eGrouped term includes feces soft and frequent bowel movements.

^fGrouped term includes abdominal pain upper, abdominal discomfort, abdominal pain lower, abdominal tenderness, and epigastric discomfort.

VORANIGO duration of exposure for safety analysis

The median duration of exposure to VORANIGO for the primary safety analysis was 12.7 months (range, 1 to 30 months).¹

Duration of exposure to VORANIGO	Number of patients
≥6 months	153 (92%)
≥1 year	89 (53%)

The most common and severe ARs in patients who received VORANIGO¹:

The most common (≥15%) ARs were fatigue (37%), COVID-19 (33%), musculoskeletal pain (26%), diarrhea (25%), and seizure (16%)
Grade 3 or 4 (≥2%) laboratory abnormalities were ALT increased (10%), AST increased (4.8%), GGT increased (3%), and neutrophil decreased (2.4%)
Serious ARs occurred in 7% of patients who received VORANIGO. The most common serious ARs occurring in ≥2% of patients who received VORANIGO includes seizure (3%)

Treatment adjustments may be needed due to adverse reactions

Learn more

The INDIGO trial assessed lab abnormalities of VORANIGO compared with placebo¹

Select laboratory abnormalities worsening from baseline occurring in ≥5% of patients¹

VORANIGO 40 mg daily (n=167)

Placebo (n=163)

Parameter	All Grades^g (%^h)	Grades^g 3 or 4 (%^h)
Chemistry		VORANIGO 40 mg daily (n=167) Placebo (n=163)
Increased ALT	59 59% 25 25%	10 10% 0 0%
Increased AST	46 46% 20 20%	4.8 4.8% 0 0%
Increased creatinine	11 11% 7 7%	0.6 0.6% 0 0%
Decreased calcium	10 10% 7 7%	0 0% 0 0%
Increased glucoseⁱ	10 10% 4.3 4.3%	0 0% 0 0%
Increased GGT	38 38% 10 10%	3 3% 1.8 1.8%
Decreased phosphate^j	8 8% 4.9 4.9%	0.6 0.6% 0 0%
Increased potassium	23 23% 20 20%	0.6 0.6% 0 0%
Increased ALP	10 10% 7 7%	1.2 1.2% 0.6 0.6%
Hematology
Increased hemoglobin	13 13% 3.1 3.1%	0 0% 0 0%
Decreased lymphocytes	11 11% 8 8%	1.8 1.8% 0.6 0.6%
Decreased leukocytes	13 13% 12 12%	0.6 0.6% 0.6 0.6%
Decreased neutrophils	14 14% 12 12%	2.4 2.4% 1.8 1.8%
Decreased platelets	12 12% 4.3 4.3%	0 0% 0 0%

^gBased on NCI CTCAE v5.0.

^hThe denominator used to calculate percentages is N, the number of subjects in the Safety Analysis Set within each treatment group.

ⁱIncludes AR term hyperglycemia.

^jIncludes AR terms hypophosphatemia and blood phosphorus decreased.

Transaminase elevations resolved to Grade 1 or baseline levels after modifying or discontinuing treatment with VORANIGO³

See VORANIGO monitoring & dosing

Learn more about dosing and administration of once-daily VORANIGO

ALP, alkaline phosphatase; ALT, alanine aminotransferase; AR, adverse reaction; AST, aspartate aminotransferase; GGT, gamma-glutamyl transferase; mIDH, mutant isocitrate dehydrogenase.

References: 1. Voranigo. Package insert. Servier Pharmaceuticals LLC; 2025. 2. Mellinghoff IK, van den Bent MJ, Touat M, et al. A global, randomized, double-blinded, Phase 3 study of vorasidenib versus placebo in patients with adult-type diffuse glioma with an IDH1/2 mutation (INDIGO): UPDATED RESULTS. Presented at: Society for Neuro-Oncology Annual Meeting; November 21-24, 2024; Houston, TX. 3. Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al. Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. N Engl J Med. 2023;389(7):589-601. doi:10.1056/NEJMoa2304194

IMPORTANT SAFETY INFORMATION

INDICATION

VORANIGO (40 mg tablets) 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.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hepatotoxicity: VORANIGO can cause hepatic transaminase elevations, which can lead to hepatic failure, hepatic necrosis, and autoimmune hepatitis. Monitor liver laboratory tests (AST, ALT, GGT, total bilirubin, and alkaline phosphatase) prior to the start of VORANIGO, every 2 weeks during the first 2 months of treatment, then monthly for the first 2 years of treatment, and as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Reduce the dose, withhold, or permanently discontinue VORANIGO based on severity.

Embryo-Fetal Toxicity: Based on findings from animal studies, VORANIGO can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective nonhormonal contraception during treatment with VORANIGO and for 3 months after the last dose, since VORANIGO can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with VORANIGO and for 3 months after the last dose.

ADVERSE REACTIONS

The most common (≥15%) adverse reactions included 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.

DRUG INTERACTIONS

Avoid concomitant use of VORANIGO with strong and moderate CYP1A2 inhibitors. Avoid concomitant use with moderate CYP1A2 inducers and smoking tobacco. Avoid concomitant use with CYP3A substrates, where a minimal concentration change can reduce efficacy. If concomitant use of hormonal contraception cannot be avoided, use nonhormonal contraception methods.

LACTATION

Advise women not to breastfeed during VORANIGO treatment and for 2 months after the last dose.

IMPAIRED FERTILITY

VORANIGO may impair fertility of females and males of reproductive potential.

Please see Full Prescribing Information.

INDIGO trial: Safety of VORANIGO® vs placebo in 330 patients with mIDH glioma1

The INDIGO trial assessed adverse reactions (ARs) of VORANIGO compared with placebo1

ARs reported in ≥5% of patients in the INDIGO trial1

VORANIGO duration of exposure for safety analysis

The most common and severe ARs in patients who received VORANIGO1:

The INDIGO trial assessed lab abnormalities of VORANIGO compared with placebo1

Select laboratory abnormalities worsening from baseline occurring in ≥5% of patients1

The information on this website is for U.S. healthcare professionals only.

You are now leaving the VORANIGO® (vorasidenib) website for U.S. healthcare professionals.

INDICATION

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

DRUG INTERACTIONS

LACTATION

IMPAIRED FERTILITY

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INDIGO trial: Safety of VORANIGO® vs placebo in 330 patients with mIDH glioma¹

The INDIGO trial assessed adverse reactions (ARs) of VORANIGO compared with placebo¹

ARs reported in ≥5% of patients in the INDIGO trial¹

The most common and severe ARs in patients who received VORANIGO¹:

The INDIGO trial assessed lab abnormalities of VORANIGO compared with placebo¹

Select laboratory abnormalities worsening from baseline occurring in ≥5% of patients¹

You are now leaving the VORANIGO^® (vorasidenib) website for U.S. healthcare professionals.