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INDIGO trial design and patient characteristics

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INDIGO trial design INDIGO trial efficacy outcomes INDIGO patient characteristics

INDIGO was a phase 3, randomized, multicenter, double-blind, placebo-controlled trial (N=331)1,2

Eligible patients
were required to:
  • Be ≥12 years of age
  • Have Grade 2 IDH1- or IDH2-mutant astrocytoma or oligodendrogliomaa
  • Have prior surgery for glioma
  • Have measurable, non-enhancing disease
  • Have not received prior anticancer treatment, including chemotherapy or radiotherapy
One to one double-blind randomization. VORANIGO 40 mg orally once daily (n equals 168). Placebo orally once daily (n equals 163). One to one double-blind randomization. VORANIGO 40 mg orally once daily (n equals 168). Placebo orally once daily (n equals 163).

Treatment continued until radiographic disease progression or unacceptable toxicity.1

Tumor assessments were performed every 12 weeks.1

aIDH1 or IDH2 mutation status was prospectively determined by the Life Technologies Corporation Oncomine Dx Target Test.1

bRandomization was stratified by local 1p/19q status (codeleted or not codeleted) and baseline tumor size (diameter ≥2 cm or <2 cm).1

INDIGO trial efficacy outcomes

Following the primary analysis data cutoff of September 6, 2022, the extended analysis includes 6 months of additional data to the date of unblinding on March 7, 2023.3

The extended analysis for progression-free survival (PFS), time to next intervention (TTNI), tumor growth rate (TGR), and seizure activity was not controlled for multiplicity.

Major efficacy outcome: PFS

The time from randomization to the date of the first documented disease progression or death due to any cause. PFS was also analyzed by subgroup. Subgroup analyses were descriptive and not powered for statistical significance2,3,c

See VORANIGO PFS results

Key secondary outcome: TTNI

The time from randomization to the initiation of the first subsequent anticancer therapy or death due to any cause1

See VORANIGO TTNI results

Other secondary outcome: TGR

The on-treatment percentage change in tumor volume every 6 months1

See VORANIGO TGR results

Exploratory outcome: Seizure activity

The number and severity of seizures were self-reported by patients using a diary during each cycle4

See VORANIGO seizure activity results

cPFS was evaluated by a blinded independent review committee (BIRC) per modified Response Assessment in Neuro-Oncology for Low Grade Glioma (RANO-LGG) criteria.1 The RANO criteria for LGGs define progressive disease as either a radiographic disease progression (a ≥25% increase in the sum of the products of perpendicular T2-weighted or T2-weighted fluid-attenuated inversion recovery), or the presence of a new lesion as a newly measurable or increased enhancement.2

INDIGO trial patient characteristics

The study population was generally balanced across treatment arms, including age, histologic subtype, and type of surgery2,5

More than 50% of patients treated with VORANIGO had gross total resection at the time of surgery

Demographic and disease characteristics VORANIGO
(n=168)		 Placebo
(n=163)
Demographics
Age
Median years (range) 40.5 (21-71) 39 (16-65)
Age distribution, %
16 or 17 years 0 0.6
18 to 39 years 45 53
40 to 64 years 54 45
≥65 years 1.2 0.6
Male sex, % 60 53
Disease characteristics
Histologic subtype, %
Oligodendroglioma (1p/19q-codeleted) 52 52
Astrocytoma (1p/19q-non-codeleted) 48 49
Number of previous surgeries for glioma, %
1 75 82
≥2 25 18
Surgery type,4 %
Biopsy 14 12
Sub-total resection 48 41
Gross total resection 51 58
IDH mutation status, %
IDH1-positived 97 93
R132H 87 85
R132C 4.8 4.3
R132G 3.0 0.6
R132L 1.2 2.5
R132S 1.2 1.2
IDH2-positive 3.0 7
R172K 1.8 6
R172G 1.2 0
R172W 0 0.6

dTwo patients in the placebo group had CDKN2A homozygous deletion.2

See efficacy results

mIDH, mutant isocitrate dehydrogenase.

References: 1. Voranigo. Package insert. Servier Pharmaceuticals LLC; 2025. 2. 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 3. US Food and Drug Administration. Center for Drug Evaluation and Research. Multidisciplinary Review for NDA 218784, Voranigo (vorasidenib). Center for Drug Evaluation and Research. Accessed September 12, 2025. www.accessdata.fda.gov/drugsatfda_docs/nda/2024/218784Orig1s000MultidisciplineR.pdf 4. 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. 5. Data on file. Servier Pharmaceuticals LLC.

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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.

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