Rhythm B V — Imcivree EMA EPAR variation assessment report (EMEA/H/C/005089, 2021)
Rhythm B V · 2021 · EMA EPAR variation assessment report
Report summary
This report summarizes a Type II variation application for IMCIVREE (setmelanotide) to expand its indication for acquired hypothalamic obesity (HO) in patients aged 4 and above. Setmelanotide, a selective MC4 receptor agonist, aims to reduce hunger and BMI, improve metabolic parameters, and increase energy expenditure. Pivotal Phase 3 study RM-493-040 demonstrated statistically significant reductions in BMI, BMI z-score, waist circumference, and hunger compared to placebo over 52 weeks. Improvements in cardiometabolic parameters and quality of life were also observed. The safety profile was consistent with known setmelanotide effects, with common adverse events including hyperpigmentation, nausea, and vomiting. Immunogenicity assessment showed no confirmed anti-setmelanotide antibodies. The report concludes with risk management plans and product information updates for the new HO indication, addressing an unmet medical need.
Key findings — cited to the page
| Estimated number of patients with acquired HO | 5,000 to 10,000 | United States · p.11 |
| Incidence peak of craniopharyngiomas in adulthood | 25% | · p.11 |
| Protocol Assistance date from CHMP | 15/12/2022 | · p.10 |
| Protocol Assistance number from CHMP | EMA/SA/0000104704 | · p.10 |
| Craniopharyngiomas as percentage of paediatric intracranial tumors | 5% to 15% | · p.11 |
| Incidence peak of craniopharyngiomas in childhood | 29% | · p.11 |
| Number of clinical sites | 35 | RM-493-040 · North America, United Kingdom, Europe, Japan · p.26 |
| Orphan medicinal product designation number | EU/3/23/2833 | IMCIVREE · EU · p.9 |
| Orphan medicinal product designation date | 13 October 2023 | IMCIVREE · EU · p.9 |
| EMA Decision number for paediatric investigation plan changes | EMA/PE/0000245434 | · p.9 |
| EMA Decision date for paediatric investigation plan changes | 06/05/2025 | · p.9 |
| Median weight in RGDO patients | 118 kg | · p.21 |
Source: Rhythm 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 Metabolic library →