Vorasidenib (dual mutant IDH1/2 inhibitor) cuts seizure rates ~80% and delays QoL decline in INDIGO grade 2 glioma

Vorasidenib (VOR) is an oral, brain-penetrant dual inhibitor of mutant IDH1/2 evaluated vs placebo in the Phase 3 INDIGO trial (NCT04164901) in treatment-naïve (post-surgery only) grade 2 mIDH1/2 diffuse glioma patients aged ≥12 with controlled baseline seizures. In this exploratory seizure/QoL analysis using pre- and post-unblinding data (placebo patients after crossover excluded), 110/331 (33.2%) reported ≥1 seizure during study; among those with seizure burden, on-treatment seizure rates were 13.2 vs 64.9 per person-year for VOR vs placebo (rate ratio 0.20; p=0.0008), and VOR delayed time to first worsening of FACT-Br (HR 0.38, p=0.0435) and the brain cancer subscale BrCS (HR 0.32, p=0.0263). In context, the “SOC” for this exact INDIGO population is typically active surveillance until progression (no systemic antiseizure benefit expected), while definitive RT+chemo is commonly deferred to avoid neurocognitive toxicity—so a pharmacologic seizure-burden reduction on top of INDIGO’s disease-control benefit (median PFS 27.7 vs 11.1 months vs placebo in the primary report) is clinically additive rather than a head-to-head vs RT/temozolomide comparison.