Merck B V — Ogsiveo EMA EPAR public assessment report (EMEA/H/C/006071, 2025)
Merck B V · 2025 · EMA EPAR public assessment report · company profile →
Report summary
The EMA's assessment of Ogsiveo (nirogacestat) for adult desmoid tumor patients led to a positive marketing authorization opinion. Ogsiveo, an orphan medicinal product, is a gamma secretase inhibitor. Its approval is supported by the pivotal Phase 3 NIR-DT-301 study, which demonstrated significant improvements in progression-free survival (71% risk reduction) and objective response rate (41% vs. 8% for placebo), alongside improved patient-reported outcomes. Quality aspects addressed manufacturing, impurity control (especially nitrosamines), and a shortened shelf-life. Non-clinical studies revealed low bioavailability, extensive metabolism, and dose-dependent toxicities. Clinically, nirogacestat exhibits extensive CYP3A4 metabolism, with a recommended 150 mg BID dose. Key safety concerns include ovarian toxicity, dermatologic reactions, hepatotoxicity, and bone fractures, necessitating a post-authorization safety study and additional monitoring.
Key findings — cited to the page
| grade 3 AST increased (placebo) | 1 % | · p.150 |
| shifts to grade 1 eosinophilia (nirogacestat) | 26 % | · p.152 |
| shifts to grade 1 eosinophilia (placebo) | 6 % | · p.152 |
| grade 3 AST increased (nirogacestat) | 3 % | · p.150 |
| grade 3 diarrhoea incidence (placebo) | 1 % | · p.151 |
| grade <= 2 diarrhoea resolved (on nirogacestat) | 74 % | · p.151 |
| probability of grade 3+ hypophosphatemia at 100 mg dose | 5.89 % | · p.55 |
| probability of grade 3+ hypophosphatemia at 150 mg dose | 6.78 % | · p.55 |
| grade 3 ALT increased (nirogacestat) | 3 % | · p.150 |
| grade 3 ALT increased (placebo) | 1 % | · p.150 |
| grade 3 diarrhoea incidence (nirogacestat) | 16 % | · p.151 |
| Orphan medicinal product designation date | 17 October 2019 | Ogsiveo · EU · p.6 |
Source: Merck B V ↗ · 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 →