Servier — Voranigo EMA EPAR public assessment report (EMEA/H/C/006284, 2025)
Servier · 2025 · EMA EPAR public assessment report
Report summary
The EMA assessed Voranigo (vorasidenib) for IDH-mutated astrocytoma or oligodendroglioma in adults and adolescents aged 12+, following surgery. Initially fast-tracked, the application reverted to standard review due to critical issues. Vorasidenib, an IDH1/2 inhibitor, demonstrated potent inhibition of mutant IDH isoforms and reduced 2-HG levels in non-clinical studies. Toxicology studies identified target organ toxicities in animals and established NOAELs. Clinical trials, particularly the pivotal Phase 3 INDIGO study, showed significant improvement in progression-free survival (PFS) for vorasidenib (median 27.7 months) versus placebo (11.1 months), with a hazard ratio of 0.39. A companion diagnostic (Oncomine DxTarget Test) is used for patient selection. The safety profile indicates higher rates of treatment-emergent adverse events (TEAEs) with vorasidenib, notably hepatotoxicity (elevated liver transaminases) and diarrhea. While most adverse events were manageable, grade ≥3 TEAEs were more frequent in the vorasidenib arm. Long-term risks, including carcinogenicity and reproductive toxicity, require ongoing monitoring.
Key findings — cited to the page
| incidence of grade ≥3 TEAEs | 22.8 % | · p.155 |
| grade ≥ 3 ALT increase | 9.6 % | · p.156 |
| Grade >=3 TEAEs (vorasidenib 40 mg QD, AG881-C-004 without crossover) | 22.8 % | AG881-C-004 · p.103 |
| Grade >=3 treatment-related TEAEs (placebo, AG881-C-004 pre-crossover) | 3.7 % | AG881-C-004 · p.103 |
| treatment-related grade ≥3 TEAEs | 13.2 % | · p.155 |
| treatment-related grade ≥3 TEAEs | 3.7 % | · p.155 |
| IDH1 mutations frequency in Grade 2 and 3 diffuse gliomas | 80 % | · p.12 |
| IDH2 mutations frequency in Grade 2 and 3 diffuse gliomas | 4 % | · p.12 |
| Grade >=3 TEAEs (placebo, AG881-C-004 pre-crossover) | 13.5 % | AG881-C-004 · p.103 |
| Grade >=3 treatment-related TEAEs (vorasidenib 40 mg QD, AG881-C-004 without crossover) | 13.2 % | AG881-C-004 · p.103 |
| incidence of grade ≥3 TEAEs | 13.5 % | · p.155 |
| grade ≥ 3 ALT increase | 0 | · p.156 |
Source: Servier ↗ · License: EMA - reuse permitted with acknowledgement. Summary and findings are extracted from the published document; every figure cites its page. Informational only — not investment advice. Explore the Oncology library →