On November 3, 2025 Servier reported longer-term data from the Phase 3 INDIGO trial evaluating VORANIGO (vorasidenib) versus placebo in patients with Grade 2 mutant isocitrate dehydrogenase 1 or 2 (mIDH1/2) glioma following surgical intervention and for whom chemoradiotherapy can be delayed were published in The Lancet Oncology. The analysis reports an additional six months of placebo-controlled, double-blind data collected between the second interim analysis data cutoff on September 6, 2022, and trial unblinding on March 7, 2023. These positive results confirm and strengthen the previous findings from the INDIGO pivotal trial.

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"These longer-term results from the INDIGO trial build upon VORANIGO’s previously demonstrated clinical benefits and demonstrate reductions in tumor volume and seizure frequency in patients with IDH-mutated gliomas," said Becky Martin, PhD, Chief of Medical, Servier Pharmaceuticals. "One year after the FDA approval of VORANIGO, we’re immensely proud to have delivered this first-of-its-kind targeted therapy to thousands of patients living with IDH-mutated glioma, offering them clinically meaningful and durable treatment benefits supported by more than a decade of research."

As of data cutoff on March 7, 2023, median follow-up was 20.1 months. Key findings from the newly published analysis include:

Median progression-free survival (PFS) improved with VORANIGO (not estimable [NE] [95% CI, 22.1-NE]) compared to placebo (11.4 [95% CI, 11.1-13.9] months), with the hazard ratio (HR) continuing to favor VORANIGO (HR, 0.35 [95% CI, 0.25-0.49]; p<0.0001*). PFS was the primary endpoint of the trial.
Imaging-based disease progression per blinded independent review committee (BIRC) occurred in 32% of patients receiving VORANIGO versus 64% receiving placebo.
Prespecified subgroup analyses continued to show that PFS per BIRC was consistent across all subgroups, favoring VORANIGO over placebo.
Median time to next intervention (TTNI) also improved with VORANIGO versus placebo (NE versus 20.1 months, respectively; HR, 0.25 [95% CI, 0.16-0.40]; p<0.0001*), reflecting durability of disease management. TTNI was a key secondary endpoint of the trial.
Treatment with VORANIGO reduced tumor growth rate and seizure frequency over placebo with no observed negative effects on health-related quality of life (HRQoL) or neurocognition.
An exploratory analysis of patients experiencing one or more seizures showed that rates of on-treatment seizures per person-year were lower in patients receiving VORANIGO (18.2 seizures per person-year [95% CI, 8.4-39.5]) than in those receiving placebo (51.2 seizures per person-year [95% CI, 22.9-114.8]; p=0.026).
The safety profile of VORANIGO was consistent with previously reported data. The most commonly reported Grade ≥3 or worse treatment-emergent adverse events (TEAEs) were increased alanine aminotransferase (10%), increased aspartate aminotransferase (5%), seizures (4%) and increased gamma-glutamyltransferase (3%). No new safety signals were detected and fewer than 5% of patients discontinued treatment due to an adverse event. There were no treatment-related deaths.
*The reported P-values are nominal and were not prespecified or adjusted for multiplicity; therefore, the results should be interpreted with caution.

"For decades, patients with Grade 2 IDH-mutated gliomas had limited treatment options. While surgery was often the first line treatment option for glioma, total resection was rarely achievable because tumors continue to grow and infiltrate the brain even after surgery," said Timothy Cloughesy, M.D., David Geffen School of Medicine, Department of Neurology, University of California, Los Angeles, investigator for the INDIGO trial. "The longer-term data from the INDIGO trial demonstrate that targeted IDH inhibition can fundamentally alter the growth trajectory of certain gliomas, leading to gradual tumor shrinkage."

These data were previously presented at the 2024 Society for Neuro-Oncology Annual Meeting (SNO). VORANIGO was approved by the U.S. Food and Drug Administration (FDA) in August 2024 after receiving Fast Track Designation and became the first and only FDA-approved targeted treatment for Grade 2 IDH-mutant glioma.

The Phase 3 INDIGO trial is ongoing. Servier plans to present longer-term follow-up results from the largest dataset to date in IDH-mutant glioma, with remarkable overall response rates and PFS outcomes not previously reported in a cohort this size.

(Press release, Servier, NOV 3, 2025, View Source [SID1234659299])