The European Commission has approved vorasidenib (Voranigo) for the treatment of adult and adolescent patients 12 years of age and older with predominantly non-enhancing grade 2 astrocytoma or oligodendroglioma harboring an IDH1 R132 or IDH2 R172 mutation who weigh at least 40 kg, only underwent surgical intervention, and are not in immediate need of radiotherapy or chemotherapy.1
This regulatory decision follows a
The approval is supported by data from the phase 3 INDIGO trial (NCT04164901).1 At a median follow-up of 14.0 months (IQR, 10.1-17.9), findings from INDIGO published in The New England Journal of Medicine demonstrated that patients who received vorasidenib (n = 168) achieved a median progression-free survival (PFS) of 27.7 months (95% CI, 17.0-not estimable) vs 11.1 months (95% CI, 11.0-13.7) among patients who received placebo (n = 163; HR, 0.39; 95% CI, 0.27-0.56; P < .001). This finding met the primary end point of the study.1,3
“Today’s EU approval of [vorasidenib] is a landmark moment for people in the [European Union (EU)] living with IDH-mutated glioma who have been waiting more than two decades for new treatment options,” Islam Hassan, MD, MSc, the global head of development (Neuro-Oncology) and senior director, LS/LCM, at Servier, stated in a news release.1 “[Vorasidenib] is the first EMA-approved therapy specifically designed to target mutant IDH enzymes in grade 2 glioma and represents a long-awaited shift in the treatment paradigm. As a leader in precision medicine, we’re grateful to the researchers, patients and advocates who have helped expand our understanding of IDH inhibition and bring this breakthrough to the EU.”
What Were the Key Design Characteristics of the INGIGO Trial?
INDIGO was international, double-blind, randomized, placebo-controlled trial that examined vorasidenib in patients with residual or recurrent grade 2 IDH-mutated glioma.3 Eligible patients needed to be at least 12 years old and have oligodendroglioma or astrocytoma harboring centrally confirmed IDH1 and IDH2 mutations. Other key eligibility criteria included a Karnofsky performance-status score of at least 80; receipt of at least 1 prior surgery, the most recent of which had to be between 1 and 5 years prior to random assignment; no other anticancer treatment for glioma; no use of glucocorticoids for signs or symptoms of glioma; a consideration of being an appropriate candidate for a watch-and-wait approach; and adequate hepatic and renal function.
Patients were randomly assigned 1:1 to receive oral vorasidenib at 40 mg once daily via continuous 28-day cycles or matching placebo. Treatment continued until disease progression, unacceptable toxicity, an indication for other anticancer therapy as determined by the investigator, or pregnancy.
The primary end point was PFS. Time to next intervention represented the key secondary end point; other secondary end points included objective response rate (ORR), tumor growth rate, health-related quality of life, overall survival, and safety.
What Safety and Additional Efficacy Data Were Seen With Vorasidenib in INDIGO?
Vorasidenib was well tolerated and its safety profile was consistent with data from phase 1 studies.1 Any-grade adverse effects (AEs) occurred in 94.6% of the safety population (n = 167).3 The most common any-grade AEs included increased alanine aminotransferase (ALT) levels (38.9%), COVID-19 (32.9%), and fatigue (32.3%). Grade 3 or higher AEs were reported in 22.8% of patients and included increased ALT levels (9.6%), increased aspartate aminotransferase levels (4.2%), seizure (4.2%), and increased γ-glutamyltransferase levels (3.0%).
Serious AEs related to vorasidenib occurred at a rate of 1.8%. AEs leading to the discontinuation of vorasidenib (3.6%) or placebo (1.2%) were reported. AEs that led to dose reductions (10.8% vs 3.1%) and interruptions (29.9% vs 22.7%) were also observed in both arms.
The median time to next intervention was not reached in the investigational arm and was 17.8 months in the placebo arm (HR, 0.26; 95% CI, 0.15-0.43; P < .001). At 18 months, the likelihood of being alive and not receiving a next treatment intervention was 85.6% (95% CI, 77.8%-90.8%) in the vorasidenib arm compared with 47.4% (95% CI, 35.8%-58.2%). At 24 months, these respective rates were 83.4% (95% CI, 74.0%-89.6%) and 27.0% (95% CI, 7.9%-50.8%). In the investigational and control arms, patients received another anticancer intervention at rates of 11.3% and 35.6%; this included patients in the placebo arm who crossed over to receive vorasidenib.
What’s Next for Vorasidenib?
Vorasidenib also holds marketing authorizations in the United States, Canada, Australia, Israel, the United Arab Emirates, Saudi Arabia, Switzerland, Brazil, the United Kingdom, and Japan.1 Additional marketing authorization applications have been submitted in several other regions, and reviews by the respective health authorities are ongoing, according to Servier.
References
- European Commission approves Servier’s VORANIGO (vorasidenib) as the first targeted therapy for grade 2 IDH-mutant glioma in the EU. News release. Servier. September 22, 2025. Accessed September 22, 2025. https://www.prnewswire.com/news-releases/european-commission-approves-serviers-voranigo-vorasidenib-as-the-first-targeted-therapy-for-grade-2-idh-mutant-glioma-in-the-eu-302562180.html
- Servier receives positive CHMP opinion for VORANIGO (vorasidenib) for the treatment of adults and adolescents with grade 2 IDH-mutant diffuse glioma. News Release. Servier. July 15, 2025. Accessed September 22, 2025. https://servier.com/en/newsroom/positive-opinion-chmp-voranigo-idh-mutant-glioma/
- Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al. Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. N Engl J Med. 2023;389(7):589-601. doi:10.1056/NEJMoa2304194