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VORANIGO® demonstrated improvements versus placebo across PFS and TTNI^1,2

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Progression-free survival Time to next intervention Tumor growth rate Seizure activity

Major efficacy outcome: Progression-free survival (PFS)

VORANIGO (vorasidenib) significantly extended PFS, giving patients with mIDH glioma more time without disease progression vs placebo¹

Primary analysis: 61% reduced risk of disease progression or death with VORANIGO vs placebo (HR=0.39; 95% CI, 0.27-0.56; P<0.0001)

Extended analysis: median PFS was not reached for VORANIGO vs 11.4 months with placebo²

At 12 months, the rate of progression-free survival for VORANIGO was 77% (vs 47% for placebo); at 24 months, it was 59% for VORANIGO (vs 26% for placebo)²

Kaplan-Meier Curve for PFS per BIRC in the INDIGO trial: extended analysis

With 6 months of additional data, the extended analysis confirmed improvement in PFS

65%

reduced risk of disease progression or death HR=0.35
(95% CI, 0.25-0.49)^2,a

Kaplan-Meier Curve for Progression-free survival (PFS) in the INDIGO trial: extended analysis.

PFS in patients with mIDH glioma

Efficacy parameter	Primary analysis¹
Efficacy parameter	VORANIGO (n=168)	Placebo (n=163)
Number of events^b n (%)	47 (28)	88 (54)
HR (95% CI)	0.39 (0.27-0.56)

Efficacy parameter	Extended analysis²
Efficacy parameter	VORANIGO (n=168)	Placebo (n=163)
Number of events^b n (%)	54 (32)	104 (64)
HR (95% CI)	0.35 (0.25-0.49)

The extended analysis for PFS was not controlled for multiplicity.

^aFollowing 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, 2023.²

^bNumber of events include progressive disease and death.¹

BIRC, blinded independent review committee; HR, hazard ratio; mIDH, mutated isocitrate dehydrogenase; mPFS, median PFS; NE, not estimable.

PFS across subgroups³

The PFS result from each subgroup appeared consistent with the overall PFS from the primary analysis, favoring VORANIGO over placebo.

These analyses are provided as descriptive clinical information only and are not intended to demonstrate efficacy in particular subgroups. These analyses were not powered for statistical hypotheses testing.

Progression-free survival across subgroups: age, chromosome 1p/19q codeletion status, location of tumor at initial diagnosis, surgical history and tumor size at baseline.

Ad hoc analysis

Additional subgroup analysis for baseline tumor volume from the extended analysis^4,d

^cAge subgroup shown include only categories with sufficient events to estimate hazard ratios.

^dData shown is based on an extended ad hoc analysis conducted after the primary study. This subgroup was not pre-specified.

^eNatural log (ln) tumor volume categories are shown. Tumor volumes of ≤2.98 cm³ correspond to ≤8, volumes of >2.98 cm³ and ≤22 cm³ correspond to >8 and ≤10, and volumes of >22 cm³ correspond to >10.

Download the VORANIGO PFS Brochure for a convenient summary of the INDIGO primary and extended PFS results and patient criteria considerations

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Secondary outcome: Time to next intervention (TTNI)

VORANIGO provided more time before subsequent treatment was initiated compared with placebo in the INDIGO trial¹

Primary analysis: Median TTNI was not reached for VORANIGO vs 17.8 months with placebo (HR=0.26; 95% CI, 0.15-0.43; P<0.0001)¹

In the extended analysis, median TTNI was not reached for VORANIGO vs 20.1 months with placebo²

Kaplan-Meier Curve for TTNI in the INDIGO trial: extended analysis

With 6 months of additional data, the extended analysis confirmed improvement in TTNI

75%

reduced risk of receiving a next intervention or death

HR=0.25

(95% CI, 0.16-0.40)^2,a

Kaplan-Meier Curve for TTNI in the INDIGO trial: extended analysis.

TTNI in patients with mIDH glioma

Efficacy parameter	Primary analysis^1,5
Efficacy parameter	VORANIGO (n=168)	Placebo (n=163)
Number of events^b n (%)	19 (11)	58 (36)
HR (95% CI)	0.26 (0.15-0.43)

Efficacy parameter	Extended analysis²
Efficacy parameter	VORANIGO (n=168)	Placebo (n=163)
Number of events^b n (%)	28 (17)	78 (48)
HR (95% CI)	0.25 (0.16-0.40)

The extended analysis for TTNI was not controlled for multiplicity.

^aTTNI was the time from randomization to the initiation of first subsequent anticancer therapy (including vorasidenib for patients randomized to placebo who subsequently crossed over to vorasidenib) or death due to any cause.³

^bNumber of events include first subsequent anticancer therapy (except crossover), crossover to VORANIGO, and death.¹

HR, hazard ratio; mIDH, mutant isocitrate dehydrogenase; mTTNI, median time to next intervention; NE, not estimable.

Watch Dr Tresa McGranahan and Dr Simon Khagi dive in to the clinical data for VORANIGO

Secondary outcome: Tumor growth rate (TGR)

TGR in the VORANIGO arm was -1.3% vs 14.4% in the placebo arm^2,a,b

Percent change in tumor volume every 6 months^a,b

	VORANIGO (n=167)	Placebo (n=161)
Tumor growth rate per BIRC (95% Cl)	-1.3% (-3.2, 0.7)	14.4% (12.0, 16.8)
Difference between slopes	15.9% (95% CI, 12.6 to 19.3)

Tumor volume change from baseline with VORANIGO vs placebo^2,c

The TGR endpoint has not been validated and the clinical significance of the changes observed is not known. This outcome was not controlled for multiplicity.

^an was the number of patients who had at least one volume record during the corresponding period.²

^bThe table depicts the TGR estimated from the linear mixed effect model, for which the treatment group, time, treatment group by time interaction, log of tumor volume at baseline, and codeletion randomization stratification stratum are fixed effects.² Tumor volume was measured per BIRC using modified RANO-LGG criteria at baseline and after randomization following a schedule of tumor assessments.

^cThe figure shows the percent change of volume from baseline plotted against time from randomization based on nonparametric LOESS regression.²

BIRC, blinded independent review committee; LOESS, locally estimated scatterplot smoothing; RANO-LGG, Response Assessment in Neuro-Oncology for Low-Grade Gliomas.

Download the VORANIGO Efficacy Highlights Brochure for a concise resource featuring the INDIGO primary and extended analyses

Download now

Exploratory outcome: Seizure activity—subgroup analysis

Among patients who reported ≥1 on-treatment seizure, the rate of seizures in the VORANIGO arm was 18.2 seizures per person-year vs 51.2 in the placebo arm^2,a,b

In the INDIGO trial, investigators reported seizures as an adverse event (AE) for all grades in 16% of patients treated with VORANIGO and 15% of patients treated with placebo¹

Seizure AEs were assessed and reported in the Prescribing Information if qualified as an AE.⁴

Subgroup analysis in patients who reported at least 1 seizure while on treatment²

Subgroup analysis in patients who reported at least one seizure while on treatment.

The seizure rate for VORANIGO was

64%

lower compared to placebo²

A rigorous statistical conclusion cannot be made because seizure activity was an exploratory outcome, and the results should be interpreted with caution. This outcome was not controlled for multiplicity.

Seizure activity was also assessed as an exploratory outcome, including the frequency, severity, and type of seizures, and changes in antiseizure medications.³

Data based on patient self-reported diary that captured the number and severity of seizures during each cycle²
Only patients with controlled seizures were included in the INDIGO trial^2,c
Antiseizure medication was prescribed at the investigator’s discretion²

^aOn-treatment seizure activity was calculated using a negative binomial model, a commonly used statistical model in epilepsy evaluations. The model was adjusted by baseline seizure number and stratification factors (chromosome 1p/19q-codeletion status and tumor size at baseline).²

^bGrouped term includes partial seizures, generalized tonic-clonic seizure, epilepsy, clonic convulsion, and simple partial seizures.¹

^cUncontrolled seizures were defined as persistent seizures interfering with activities of daily life and failed 3 lines of antiepileptic drug regimens including at least 1 combination regimen.⁵

See the safety profile of VORANIGO

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. 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. Data on file. Servier Pharmaceuticals LLC. 5. 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.

VORANIGO® demonstrated improvements versus placebo across PFS and TTNI1,2

VORANIGO (vorasidenib) significantly extended PFS, giving patients with mIDH glioma more time without disease progression vs placebo1

Kaplan-Meier Curve for PFS per BIRC in the INDIGO trial: extended analysis

With 6 months of additional data, the extended analysis confirmed improvement in PFS

65%

reduced risk of disease progression or death HR=0.35(95% CI, 0.25-0.49)2,a

PFS in patients with mIDH glioma

PFS across subgroups3

Additional subgroup analysis for baseline tumor volume from the extended analysis4,d

VORANIGO provided more time before subsequent treatment was initiated compared with placebo in the INDIGO trial1

Kaplan-Meier Curve for TTNI in the INDIGO trial: extended analysis

With 6 months of additional data, the extended analysis confirmed improvement in TTNI

75%

reduced risk of receiving a next intervention or death

HR=0.25

(95% CI, 0.16-0.40)2,a

TTNI in patients with mIDH glioma

Watch Dr Tresa McGranahan and Dr Simon Khagi dive in to the clinical data for VORANIGO

TGR in the VORANIGO arm was -1.3% vs 14.4% in the placebo arm2,a,b

Percent change in tumor volume every 6 monthsa,b

Tumor volume change from baseline with VORANIGO vs placebo2,c

Among patients who reported ≥1 on-treatment seizure, the rate of seizures in the VORANIGO arm was 18.2 seizures per person-year vs 51.2 in the placebo arm2,a,b

In the INDIGO trial, investigators reported seizures as an adverse event (AE) for all grades in 16% of patients treated with VORANIGO and 15% of patients treated with placebo1

Subgroup analysis in patients who reported at least 1 seizure while on treatment2

The seizure rate for VORANIGO was

64%

lower compared to placebo2

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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VORANIGO® demonstrated improvements versus placebo across PFS and TTNI^1,2

VORANIGO (vorasidenib) significantly extended PFS, giving patients with mIDH glioma more time without disease progression vs placebo¹

reduced risk of disease progression or death HR=0.35
(95% CI, 0.25-0.49)^2,a

PFS across subgroups³

Additional subgroup analysis for baseline tumor volume from the extended analysis^4,d

VORANIGO provided more time before subsequent treatment was initiated compared with placebo in the INDIGO trial¹

(95% CI, 0.16-0.40)^2,a

TGR in the VORANIGO arm was -1.3% vs 14.4% in the placebo arm^2,a,b

Percent change in tumor volume every 6 months^a,b

Tumor volume change from baseline with VORANIGO vs placebo^2,c

Among patients who reported ≥1 on-treatment seizure, the rate of seizures in the VORANIGO arm was 18.2 seizures per person-year vs 51.2 in the placebo arm^2,a,b

In the INDIGO trial, investigators reported seizures as an adverse event (AE) for all grades in 16% of patients treated with VORANIGO and 15% of patients treated with placebo¹

Subgroup analysis in patients who reported at least 1 seizure while on treatment²

lower compared to placebo²

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