EP1002 - ECE_3406 - Real-world BMI outcomes in adult patients with acquired hypothalamic obesity treated with setmelanotide for up to 9 months in France

Abstract

Acquired hypothalamic obesity (aHO) arises from physical injury to the hypothalamus caused by trauma, tumours, treatment-related damage, inflammation, or developmental abnormalities, leading to disrupted melanocortin-4 receptor (MC4R) signalling and marked by accelerated, sustained weight gain. In a 52-week placebo-controlled Phase 3 trial of the MC4R agonist setmelanotide in patients with aHO aged ≥4 years, the primary endpoint of percent change in body mass index (BMI) at Week 52 was achieved with a 16.5% reduction in the setmelanotide group corresponding to a −19.8% placebo-adjusted difference. Here, we report real-world data from 56 adult patients with aHO treated with setmelanotide for up to 9 months under France's pre-marketing early-access program. BMI outcomes and response rates—defined as achieving a ≥10% reduction—are presented for adult patients with aHO in France receiving early-access treatment with setmelanotide for up to 9 months. Fifty-six adult patients (33 females), aged 18-68 years old, started setmelanotide treatment. Forty-two patients had craniopharyngioma, 5 astrocytoma, 2 Langerhans cell histiocytosis, and 1 each hamartoma, germinoma, histiocytosis, neuroglial tumour, Rathke's pouch cyst, macroprolactinoma or not specified. Patients started treatment at 0.25-2 mg/day, titrated up to 1-3 mg/day at last included visit. For patients with 6-month data (n = 26), mean (SD) BMI at baseline was 44.8 (11.4) kg/m2 which reduced to 39.1 (12.5) kg/m2 after 6 months of treatment, representing a 12.7% decrease from baseline (P < .0001). For patients with 9-month data (n = 16), mean (SD) BMI at baseline was 42.8 (7.7) kg/m2 which decreased to 34.8 (8.5) kg/m2 after 9 months of treatment, representing an 18.7% decrease from baseline (P < .0001). Fifteen of 26 patients (57.7%) had a BMI reduction of ≥10% after 6 months of treatment. This increased to 11 of 16 patients (68.8%) after 9 months of treatment. No new safety concerns were observed and reported adverse events were consistent with phase 3 trial data. This real-world evidence of 56 patients with aHO, who received up to 9 months of setmelanotide under pre-marketing early access authorization in France showed consistent improvements in BMI. Efficacy and safety outcomes are consistent with Phase 3 trial data. These findings underscore the real-world therapeutic value of setmelanotide as an intervention strategy for patients with aHO.