On August 6, 2024, the FDA approved vorasidenib (Voranigo; Servier Pharmaceuticals LLC), an isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) inhibitor, for adult and pediatric patients 12 years and older. This is the first approval by the FDA of a systemic therapy for patients with grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation.
Efficacy was evaluated in 331 patients with grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation following surgery enrolled in INDIGO (NCT04164901), a randomized, multicenter, double-blind, placebo-controlled trial. Patients were randomized 1:1 to receive vorasidenib 40 mg orally once daily or placebo orally once daily until disease progression or unacceptable toxicity. IDH1 or IDH2 mutation status was prospectively determined by the Life Technologies Corporation Oncomine Dx Target Test. Patients who had been randomly assigned to placebo were allowed to cross over to vorasidenib after documented radiographic disease progression.
The major efficacy outcome measure was PFS using a blinded independent review committee per modified Response Assessment in Neuro-Oncology for Low Grade Glioma (RANO-LGG) criteria. An additional efficacy outcome measure was time to next intervention. The HR for PFS was 0.39 (95% CI, 0.27-0.56; P<.0001). The median time to next intervention was not reached for the vorasidenib arm and was 17.8 months for the placebo arm (HR, 0.26; 95% CI, 0.15-0.43; P<.0001).
Commonly reported (≥15%) adverse reactions included fatigue, headache, COVID-19 infection, musculoskeletal pain, diarrhea, nausea, and seizure. The most common grade 3 or 4 laboratory abnormalities (>2%) were increased alanine aminotransferase, increased aspartate aminotransferase, increased gamma-glutamyl transferase, and decreased neutrophils.
The recommended vorasidenib dose in 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 based on body weight:
- Patients weighing ≥40 kg:40 mg orally once daily.
- Patients weighing <40 kg:20 mg orally once daily.1
Editor’s note: This report was based on statements issued by the FDA and pharmaceutical companies mentioned in the approvals.
References
- Food and Drug Administration. FDA approves vorasidenib for grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. August 6, 2024. Accessed August 20, 2024. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vorasidenib-grade-2-astrocytoma-or-oligodendroglioma-susceptible-idh1-or-idh2-mutation