FDA Approves Vorasidenib for Patients With IDH1/IDH2-Mutated Grade 2 Astrocytoma or Oligodendroglioma

On August 6, 2024, the US Food and Drug Administration (FDA) approved vorasidenib, an isocitrate dehydrogenase-1 (IDH1) and IDH2 inhibitor, for adult and pediatric patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation following surgery including biopsy, sub-total resection, or gross total resection. This is the first approval of a systemic therapy for patients with Grade 2 astrocytoma or oligodenroglioma with a susceptible IDH1 or IDH2 mutation. This regulatory decision was based on results from the phase 3 INDIGO trial.

In this multicenter, double-blind, placebo-controlled trial, 331 patients were randomized on a 1-to-1 basis to receive either 40 mg of vorasidenib or placebo once daily until disease progression or unacceptable toxicity. IDH1 or IDH2 status was determined using the Oncomine Dx Target Test. Patients randomized to placebo were allowed to cross over to vorasidenib after documented radiographic disease progression. Patients who received prior anti-cancer treatment including chemotherapy or radiation therapy were excluded. The major efficacy outcome measure was progression-free survival (PFS) assessed via blinded independent central review committee.  A key secondary outcome measure was time to next intervention. 

At analysis, the hazard ratio (HR) for PFS was 0.39 (95% confidence interval [CI], 0.27 to 0.56; P < .0001).  The median time to next intervention was not reached in the vorasidenib arm and was 17.8 months in the placebo arm (HR 0.26; 95% CI, 0.15 to 0.43; P < .0001). The most common adverse reactions occurring in ≥ 15% of patients included fatigue, headache, COVID-19 infection, musculoskeletal pain, diarrhea, nausea, and seizure. The most common grade 3/4 laboratory abnormalities occurring in > 2% of patients included increased alanine aminotransferase, increased aspartate aminotransferase, increased GGT, and decreased neutrophil count. 

The recommended vorasidenib dose for adult patients is 40 mg orally once daily until disease progression or unacceptable toxicity. The recommended vorasidenib dose in pediatric patients 12 years and older is 40 mg for patients weighing ≥ 40 kg and 20 mg for patients weighing < 40 kg. 

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FDA approves vorasidenib for Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. Accessed on August 6, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vorasidenib-grade-2-astrocytoma-or-oligodendroglioma-susceptible-idh1-or-idh2-mutation