Voranigo

Grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 (IDH1) or IDH2 mutation, as detected by an FDA-approved test, in adults following a prior surgery that included biopsy, subtotal resection, or gross total resection.

40 mg orally once daily until disease progression or unacceptable toxicity
Take with or without food
Swallow whole; do not crush, break, or chew
Dose reduction: 20 mg once daily
Strong CYP3A inhibitors: Avoid; if unavoidable, reduce to 20 mg daily
Hepatic monitoring: LFTs before treatment, q2w × first 3 months, then q4w × 3 months, then periodically

Tablets: 40 mg

None listed.

• Hepatotoxicity: ALT/AST elevation in 47% (Grade 3+: 9.6%). Median onset: ~2 months. Monitor LFTs frequently. Withhold for ALT/AST >5× ULN or >3× with bilirubin >2×. Permanently D/C for recurrent Grade 3+ or Hy's law criteria.
• Embryo-Fetal Toxicity: Can cause fetal harm based on mechanism and animal data.

Fatigue (27%), headache (23%), COVID-19 (23%), musculoskeletal pain (22%), diarrhea (18%), nausea (18%), seizure (15%), ALT increase (47%), AST increase (42%), GGT increase (36%), decreased appetite (10%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Vorasidenib is a dual inhibitor of mutant IDH1 and mutant IDH2 enzymes, designed with brain penetrance. IDH1/2 mutations (R132H, R132C, R172K, etc.) are present in >80% of grade 2-3 gliomas and produce the oncometabolite D-2-hydroxyglutarate (2-HG), which drives epigenetic dysregulation and tumorigenesis. By inhibiting mutant IDH1 and IDH2, vorasidenib reduces intratumoral 2-HG levels, allowing restoration of normal cellular differentiation and epigenetic regulation. It was specifically designed to cross the blood-brain barrier and was the first IDH inhibitor approved for gliomas.

Tmax: 2-4 hours. Half-life: approximately 80-100 hours (long). Protein binding: >99%. CNS penetrance: demonstrated brain/plasma ratio in preclinical studies. Metabolized by CYP3A4. Steady-state: ~3 weeks. Excreted in feces (>70%).

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• INDIGO — Vorasidenib vs. placebo in IDH-mutant grade 2 glioma after surgery. Phase III, n=331.
  🔬 NCT04164901 ↗ 📄 Primary Publication ↗

Voranigo has FDA-approved indications across the following cancer types covered on PipelineEvidence: