IDH1/2-Mutant Grade 2 Glioma |
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The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the approval of vorasidenib (Voranigo) for the treatment of predominantly non-enhancing grade 2 astrocytoma or oligodendroglioma with an IDH1 R132 or IDH2 R172 mutation in adult and adolescent patients aged 12 years and older who have undergone surgical resection and are not in immediate need of radiotherapy or chemotherapy.1
The CHMP recommendation is supported by findings from the phase 3 INDIGO trial (NCT04164901), a global, randomized, double-blind, placebo-controlled study evaluating vorasidenib in 331 patients with residual or recurrent grade 2 IDH-mutant glioma following surgery. 1,2
Results published in The New England Journal of Medicine showed that vorasidenib significantly improved progression-free survival (PFS) compared with placebo, with a median PFS of 27.7 months vs 11.1 months, respectively (hazard ratio [HR], 0.39; 95% CI, 0.27-0.56; P < .001).2 Time to next intervention was also significantly delayed with vorasidenib (HR, 0.26; 95% CI, 0.15-0.43; P < .001).2
Grade 3 or higher adverse effects occurred in 22.8% of patients receiving vorasidenib vs 13.5% in the placebo group. Elevated alanine aminotransferase levels of grade 3 or higher were reported in 9.6% of patients receiving vorasidenib and in none of the placebo-treated patients. No treatment-related deaths were reported.
“Today’s recommendation for European Union [EU] approval brings us one step closer to offering [vorasidenib] to patients in the EU with grade 2 IDH-mutant glioma who have historically had limited treatment options for this relentless disease,” Susan Pandya, MD, vice president of Clinical Development and global head of oncology LS/LCM, at Servier, said in a news release.1
The marketing authorization application for vorasidenib will now be reviewed by the European Commission. If approved, vorasidenib would represent the first targeted therapy option in the EU for patients with grade 2 IDH-mutant diffuse glioma.
INDIGO Study Design
In the phase 3, double-blind INDIGO trial, patients with residual or recurrent grade 2 IDH-mutant glioma who had undergone surgery as their only prior treatment were enrolled.2 As of March 7, 2023, 331 patients were randomized globally to receive vorasidenib 40 mg daily (n=168) or placebo (n=163) continuously in 28-day cycles. Of the 331 patients, 172 had oligodendroglioma (88 vorasidenib; 84 placebo) and 159 patients had astrocytoma (80 vorasidenib; 79 placebo).
The study’s primary end point was PFS. A key secondary end point was the time to the next anticancer intervention. Other secondary end points were objective response rate, tumor growth rate by volume, overall survival, and safety.
Crossover from placebo to vorasidenib was permitted upon confirmation of imaging-based disease progression. Safety outcomes were also evaluated throughout the study.
Current Indications for Vorasidenib
Currently, vorasidenib is the first and only approved therapy designed to target mutant IDH enzymes in grade 2 glioma.1
This positive recommendation follows similar regulatory stances, including the August 6, 2024, FDA approval of vorasidenib for the treatment of IDH1/2-mutant grade 2 diffuse glioma following surgical resection. In addition to its approval in the United States, vorasidenib has also been granted marketing authorization in countries such as Canada, Australia, Israel, the United Arab Emirates, Saudi Arabia, and Switzerland.
“We look forward to continuing conversations with the EMA and other regulatory bodies around the world to introduce [vorasidenib] as a potential new standard of care for patients with IDH-mutant gliomas,” Pandya concluded.
References
- Servier receives positive CHMP opinion for VORANIGO® (vorasidenib) for the treatment of adults and adolescents with grade 2 IDH-mutant diffuse glioma. News Release. Pr Newswire. Accessed July 25, 2025. https://servier.com/en/newsroom/positive-opinion-chmp-voranigo-idh-mutant-glioma/
- Mellinghoff IK, Martin, Blumenthal DT, et al. Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. The New England Journal of Medicine. 2023;389(7). doi:0.1056/nejmoa2304194