FDA approves vorasidenib for Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation
Regulatory approval: On Aug 6, 2024, the FDA approved vorasidenib (Voranigo), an IDH1/IDH2 inhibitor, for adult and pediatric patients ≥12 years with Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation following surgery. Approval was supported by the phase 3 INDIGO trial (NCT04164901), which showed improved PFS (HR 0.39) and time to next intervention (HR 0.26) versus placebo. Common AEs included fatigue and headache; notable lab abnormalities included transaminase elevations.
FDA approval (2024-08-06)
The US Food and Drug Administration (FDA) approved vorasidenib (Voranigo; Servier Pharmaceuticals LLC), an IDH1/IDH2 inhibitor, for adult and pediatric patients aged 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation, following surgery (biopsy, sub-total resection, or gross total resection). This is described as the first FDA approval of a systemic therapy for this molecularly defined Grade 2 glioma population.
Supporting trial evidence
Approval was based on INDIGO (NCT04164901), a randomized, multicenter, double-blind, placebo-controlled trial in 331 patients with susceptible IDH1/IDH2-mutant Grade 2 astrocytoma or oligodendroglioma after surgery. Patients were randomized 1:1 to vorasidenib 40 mg orally once daily or placebo until progression or unacceptable toxicity; placebo crossover to vorasidenib was permitted after radiographic progression. Prior chemotherapy or radiation therapy was excluded. Mutation status was prospectively determined with the Oncomine Dx Target Test.
Primary endpoint PFS (blinded independent review; modified RANO-LGG) showed HR 0.39 (95% CI 0.27–0.56; p<0.0001). Time to next intervention was not reached with vorasidenib vs 17.8 months with placebo (HR 0.26; 95% CI 0.15–0.43; p<0.0001).
Safety and dosing (per FDA notice)
Common (≥15%) adverse reactions: fatigue, headache, COVID-19 infection, musculoskeletal pain, diarrhea, nausea, seizure. Common grade 3/4 lab abnormalities (>2%): increased ALT, AST, GGT, and decreased neutrophils.
Recommended dosing: adults 40 mg once daily; pediatric (≥12 years) ≥40 kg: 40 mg daily; <40 kg: 20 mg daily.
Review was conducted under Project Orbis; reviews at partner agencies were ongoing at the time of the FDA communication.