Vorasidenib — Drug Monograph
Brand names: Voranigo
Drug class: Other
Mechanism of Action
Brain-penetrant dual inhibitor of mutant IDH1 and IDH2 enzymes. Blocks production of the oncometabolite 2-hydroxyglutarate (2-HG) in tumor cells, reversing epigenetic dysregulation driven by 2-HG accumulation. Designed for CNS penetration, enabling therapeutic concentrations in brain tumor tissue. First targeted therapy approved specifically for low-grade glioma.
FDA Indications
- Grade 2 IDH-mutant astrocytoma or oligodendroglioma in adults with residual or recurrent disease following surgery, not requiring immediate chemotherapy or radiotherapy (FDA approved August 2024; INDIGO trial: PFS HR 0.39 vs placebo; median PFS not reached vs 11.1 months)
Common Side Effects
- Fatigue (26%)
- Headache (19%)
- Nausea (18%)
- ALT/AST elevation (~40% any grade)
- Musculoskeletal pain
- COVID-19 infection
- Seizure (7% — likely related to underlying disease)
Clinical Pearl
Vorasidenib is the first FDA-approved therapy specifically for low-grade IDH-mutant glioma, filling a major unmet need in a disease previously managed with watch-and-wait after surgery. The INDIGO trial showed a striking 61% reduction in progression risk. Hepatotoxicity is the main safety concern and requires vigilant LFT monitoring especially in the first 6 months.