Endocrine Abstracts

Objective: To report hunger-related results from a Phase 2 trial of setmelanotide in patients with hypothalamic obesity (HO).

Methods: A Phase 2, open-label, 16-week trial of setmelanotide in patients aged ≥6 to ≤ 40 years with body mass index (BMI) ≥95th percentile (aged <18 years) or ≥35 kg/m² (aged ≥18 years) and HO caused by hypothalamic damage secondary to brain tumor, surgical resection, and/or chemotherapy was performed. The primary endpoint was the proportion of patients reaching ≥5% BMI reduction from baseline at Week 16. Change from baseline in daily hunger scores was a secondary endpoint. A daily hunger questionnaire was completed before morning meal (ie, while fasted) and setmelanotide administration each morning. Patients aged ≥12 years rated their past 24-hour hunger on an 11-point numerical rating scale, where 0 = not hungry at all and 10 = hungriest possible, with 3 questions assessing maximal, average, and morning hunger; patients aged <12 years used a pictorial version of the scale. Daily hunger scores were averaged weekly and compared with baseline score, calculated as the average of the 7 days before setmelanotide initiation. Hunger analyses were stratified by age (<12 and ≥12 years).

Results: Eighteen (13 pediatric, 5 adult) patients were included in the study. At Week 16, most (16/18) patients met the primary endpoint (88.9% [90% confidence interval, 69.0%-98.0%]; P<0.0001), with a mean percent change in BMI of −14.9% in all patients adhering to treatment administration (n=17). In patients aged ≥12 years (n=11), the mean (standard deviation [SD]) change from baseline in maximal daily hunger score was −2.9 (2.3) (percent change, −45.0% [36.3%]), in average hunger score was −3.1 (2.0) (percent change, −56.7% [35.4%]), and in morning hunger score was −2.7 (1.9) (percent change, −65.3% [35.2%]). Baseline maximal hunger scores ranged from 5.8 to 7.5; decreases were seen independent of baseline score. In patients aged <12 years (n=5), the mean change from baseline in daily hunger score was −1.4 (−62.0%). Treatment-related adverse events occurred in 18 patients (100%); nausea (n=11; 61.1%), skin hyperpigmentation (n=6; 33.3%), vomiting (n=6; 33.3%), diarrhea (n=4; 22.2%), and COVID-19 (n=4; 22.2%) were most frequently reported.

Conclusions: Patients with HO had reductions in hunger scores across all domains. These findings support continued development of setmelanotide for treatment of HO; a Phase 3 trial will begin in early 2023.