VORASIDENIB
IDH-MUTANT GRADE 2 GLIOMA
The first oral targeted therapy approved specifically for grade 2 IDH-mutant glioma — delaying tumour progression and the need for radiotherapy after surgery.
analyticsAt a Glance
- check_circleFDA-approved August 2024 for grade 2 IDH1/2-mutant astrocytoma and oligodendroglioma after surgery
- check_circleINDIGO trial: 61% reduction in risk of progression or death vs placebo (HR 0.39)
- check_circleOral daily tablet — unlike IV IDH inhibitors used in AML
- check_circleCancerFax can guide eligibility assessment and access to vorasidenib via international routes
What Is Vorasidenib and How Does It Work?
Vorasidenib (brand name Voranigo, developed by Servier) is a small-molecule inhibitor that blocks both mutant IDH1 and IDH2 enzymes. It is the first targeted oral therapy approved specifically for patients with grade 2 IDH-mutant glioma — a major advance for a disease that previously had no approved non-surgical post-operative therapy.
“By inhibiting mutant IDH, vorasidenib blocks the production of 2-hydroxyglutarate — the oncometabolite that drives the epigenetic dysregulation underlying IDH-mutant glioma growth.”
Mechanism of Action
Mutant IDH1/2 enzymes produce 2-hydroxyglutarate (2-HG), which inhibits histone and DNA demethylases, locking tumour cells in a proliferative state. Vorasidenib binds and inhibits both IDH1 R132 and IDH2 R140/R172 mutant forms, suppressing 2-HG production.
Brain Penetrance — The Key Differentiator
Unlike enasidenib and ivosidenib (IDH inhibitors used in AML), vorasidenib is specifically engineered for CNS penetrance — it crosses the blood-brain barrier at therapeutic concentrations, which is essential for treating glioma.
INDIGO Trial — Key Results at a Glance
The phase III INDIGO trial randomised 331 patients with grade 2 IDH-mutant glioma (after surgery, without prior radiotherapy or chemotherapy) to vorasidenib 40 mg daily or placebo.
- HR 0.39Progression-Free Survival Hazard Ratio61% reduction in risk of progression or death — the primary endpoint, met with high statistical significance (p<0.001).
- 27.7 moMedian PFS — Vorasidenib armCompared to 11.1 months in the placebo arm. More than doubling of progression-free survival.
- 83%Reduction in time to next treatmentSecondary endpoint: vorasidenib significantly delayed the need for subsequent radiotherapy or chemotherapy.
INDIGO Trial — Study Design and Patient Population
Understanding who was enrolled in INDIGO is critical for interpreting which patients benefit most from vorasidenib.
| Parameter | Detail |
|---|---|
| Trial phase | Phase III, randomised, double-blind, placebo-controlled |
| N enrolled | 331 patients (168 vorasidenib / 163 placebo) |
| Eligible tumour types | Grade 2 IDH1/2-mutant astrocytoma OR oligodendroglioma |
| Prior treatment | Surgery only — no prior RT or chemotherapy |
| Timing post-surgery | Residual or recurrent measurable disease; watchful waiting cohort eligible |
| IDH1 mutations | ~90% of patients — IDH1 R132H predominant |
| Primary endpoint | Progression-free survival (central radiology review) |
| Publication | Mellinghoff et al, NEJM 2023; FDA approval August 2024 |
Who Qualifies for Vorasidenib and How to Access It
Vorasidenib eligibility requires meeting specific molecular and clinical criteria. The access pathway depends on geography — the drug is FDA-approved in the US but is being sought via regulatory pathways or trials in other regions.
- 1
Confirm IDH Mutation Status
IDH1 or IDH2 mutation must be confirmed by IHC, PCR, or next-generation sequencing on tumour tissue. IDH-wildtype tumours do not respond.
- 2
Confirm Grade 2 Histology
WHO 2021 grade 2 designation required — vorasidenib is not currently approved for grade 3 tumours, though trials in this setting are active.
- 3
Post-Surgery, No Prior RT/Chemo
The INDIGO trial enrolled patients who had surgery but had not yet received radiotherapy or chemotherapy. Patients who have already received prior treatment may not be eligible for the approved indication.
- 4
Access Route — USA
Voranigo (vorasidenib) 40 mg tablets are commercially available in the US. Prescription through a neuro-oncologist or neurologist managing the case.
- 5
Access Route — International (via CancerFax)
Outside the US, access is via named patient programs, clinical trials, or regulatory submissions in progress. CancerFax maps the current access landscape and connects patients with centres actively prescribing vorasidenib.
Vorasidenib vs Watchful Waiting — The Treatment Decision
For many grade 2 glioma patients after surgery, watchful waiting (observation without treatment) has been standard. Vorasidenib changes this paradigm — but the decision to treat still involves trade-offs.
Vorasidenib (Treat Now)
- 61% PFS improvement (INDIGO)Meaningfully delays tumour progression and extends the time before needing radiotherapy or chemotherapy.
- Delays neurotoxic RTPostponing radiotherapy preserves cognitive function — a critical quality-of-life consideration in young patients.
- Oral, generally well toleratedThe main toxicity is elevated liver enzymes (ALT/AST), which is reversible and manageable with dose adjustment.
Watchful Waiting
- Avoids drug exposure and costVorasidenib is a long-term daily oral therapy — cost and drug access are relevant for many international patients.
- RT + chemotherapy remains effective at progressionGrade 2 glioma is still highly treatment-responsive — some oncologists prefer to preserve RT for progression rather than delaying it with a targeted agent.
- Long-term OS impact not yet confirmedThe INDIGO trial did not show an overall survival difference (data immature) — OS benefit remains to be established with longer follow-up.
Frequently Asked Questions
Key questions from patients and oncologists navigating vorasidenib eligibility and access.
Is vorasidenib the same as ivosidenib or enasidenib?
No. Ivosidenib (IDH1 inhibitor) and enasidenib (IDH2 inhibitor) are used in IDH-mutant acute myeloid leukaemia and cholangiocarcinoma — they are not CNS-penetrant. Vorasidenib is specifically designed to cross the blood-brain barrier and is approved for glioma, not haematological malignancies.
What are the main side effects of vorasidenib?
The most clinically significant side effect is elevated liver transaminases (ALT/AST) — observed in ~9% of patients at Grade 3+ levels in INDIGO. This is generally reversible with dose interruption or reduction. Other side effects include fatigue and headache. Liver function monitoring is required during treatment.
Can vorasidenib be used for oligodendroglioma specifically?
Yes — oligodendroglioma is IDH-mutant by definition, and the FDA approval covers both IDH-mutant astrocytoma and oligodendroglioma (grade 2). In INDIGO, ~20% of enrolled patients had oligodendroglioma and showed benefit consistent with the overall population.
Is vorasidenib available outside the US?
As of 2024–2025, vorasidenib is FDA-approved in the US but undergoing regulatory review elsewhere. Access in other countries is possible via named patient programs, compassionate use applications, or enrolment in active trials. CancerFax can identify the current access route for your country.
More from the Brain Tumour Treatment Guide
Explore related guides on glioma diagnosis, treatment options, and specialist access.
How CancerFax Helps
CancerFax is a specialist cancer access and patient-navigation platform. We help patients and families understand their options, organise medical records, coordinate hospital communication, and support cross-border treatment planning where appropriate.
We help collect and organise reports, scans, pathology, biomarker results, and treatment history for structured case review.
We communicate with hospitals or trial teams to assess whether a case may be suitable for further screening.
We support appointment coordination, document submission, translation, and direct communication with international departments.
For international patients, we help with practical coordination — travel planning, hospital admission guidance, and local support.
If this option is not suitable, we help explore other relevant treatments, clinical trials, or advanced care pathways.
From inquiry through to follow-up, our coordinators provide a single point of contact for the family.
CancerFax does not guarantee treatment access, eligibility, or clinical outcome. Our role is to help patients access accurate information, structured review, and appropriate specialist pathways.
Does Your Glioma Qualify for Vorasidenib?
Vorasidenib eligibility requires confirmed IDH1 or IDH2 mutation and WHO grade 2 histology. CancerFax reviews your molecular pathology report to determine eligibility, identify access routes, and connect you with centres offering vorasidenib or active INDIGO-aligned trials.
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified oncologist before making treatment decisions.