FDA Approval Summary: Vorasidenib for <i>IDH</i> -Mutant Grade 2 Astrocytoma or Oligodendroglioma Following Surgery
Michael I. Barbato, Amy Barone, Stephanie Aungst, Claudia P. Miller, Suryatheja Ananthula, Youwei Bi, Yuching Yang, Xiaoxue Li, Ye Xiong, Jianghong Fan, Sarah E. Dorff, Hong Zhao, Hua Zhou, Shan Pradhan, Barbara Scepura, A. K. Sinha, Maritsa Stephenson, Vishal Bhatnagar, Haleh Saber, Nam Atiqur Rahman, Shenghui Tang, Richard Pazdur, Paul G. Kluetz, Erin Larkins, Nicole Drezner
Abstract
On August 6, 2024, the FDA granted traditional approval to vorasidenib (Voranigo, Servier Pharmaceuticals, LLC) for the treatment of adult and pediatric patients 12 years and older with grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase 1 or 2 mutation following surgery, including biopsy, subtotal resection, or gross total resection. The approval was based on data from a randomized, multicenter, double-blind trial of vorasidenib compared with placebo. The primary objective was to demonstrate the efficacy of vorasidenib based on radiographic progression-free survival (PFS) per blinded independent central review according to the modified Response Assessment for Neuro-oncology for Low-Grade Gliomas criteria. PFS was assessed in 331 patients, and the HR was 0.39 (95% confidence interval, 0.27-0.56; P value < 0.0001). The most common (≥15%) adverse reactions included fatigue, headache, COVID-19, musculoskeletal pain, diarrhea, nausea, and seizure. PFS was considered an appropriate endpoint for this disease, considering the long natural history and the randomized design allowed for the interpretation of the treatment effect in this rare malignancy. This was the first FDA approval for a targeted therapy for isocitrate dehydrogenase-mutant grade 2 gliomas.