ESPE Abstracts

Introduction: Hypothalamic obesity (HO) is caused by physical, tumour- and/or treatment-related damage or developmental abnormalities to the hypothalamus which can lead to an impairment of the melanocortin-4 receptor (MC4R) signalling pathway. It is characterized by excessive and rapid weight gain following the damage. Treatment of HO with the MC4R agonist setmelanotide resulted in consistent and clinically meaningful responses in a 16-weeks open-label trial, which were maintained or increased through 12 months of follow up. Here, we report 3-months data of two paediatric patients with HO treated with setmelanotide in France under pre-marketing early access authorization.

Methods: Paediatric patients with HO were under early access treatment with setmelanotide in two different hospitals in France. This analysis reports hunger scores (4 questions, maximum total score of 40 for most hunger), weight-related outcomes and adverse events for patients with 3-months of treatment data.

Results: Two patients, both males, started setmelanotide treatment at an age of 13 years. One of them was diagnosed with craniopharyngioma and hypopituitarism, had a surgical resection and was on ongoing semaglutide treatment. The other patient had a diagnosis of chiasmatic pilocytic astrocytoma treated with proton therapy. He developed post-proton therapy radionecrosis complicated by hypothalamic syndrome with rapid onset of hyperphagia and obesity, behavioural disorders, diabetes insipidus and hypothyroidism and was on ongoing desmopressin, levothyrox, bevacizumab, hydrocortisone, and risperidone treatment. Patients started treatment at 0.5/1.0 mg setmelanotide per day and were up-titrated to 3 mg per day at Month 3. Hunger scores were on average 15.5 (standard deviation 10.5) at baseline and patients weighed on 102.2 (13.8) kg with a BMI z-score of 3.4 (0.3). After 3 months of treatment, hunger scores decreased to 12.0 (4.0) with a 6.9% decrease in weight to 95.3 (14.3) kg and a BMI z-score of 3.2 (0.4). During treatment, patients reported abdominal pain, microvesicular eruption of hair follicles on all four limbs and trunk, and induration at injection site.

Conclusion: This real-world data of 2 paediatric patients with HO who received 3 months of setmelanotide under pre-marketing early access authorization in France showed improvements in hunger scores and weight outcomes with no new safety signals.