BACKGROUND: Acquired hypothalamic obesity (HO) is a rapid-onset, severe obesity caused by hypothalamic injury that may impair melanocortin-4 receptor (MC4R) pathway signaling and lead to hyperphagia, decreased energy expenditure, and severe obesity, for which no approved therapies exist. We describe experiences or caregiver observations of hunger, weight, and energy in patients with HO before and after investigational treatment with the MC4R agonist setmelanotide.
METHODS: In-depth qualitative interviews were conducted via Zoom by 2 members of the study team with patients or caregivers of patients who completed a Phase 2 trial of setmelanotide (NCT04725240) and enrolled in the open-label long-term extension (NCT03651765). Eligible patients were aged ≥12 years and eligible caregivers were aged ≥18 years and full-time caregivers of patients aged <12 years or unable to self-report. Interview transcripts were analyzed using a thematic approach.
RESULTS: Five participants (3 patients, 2 caregivers) completed interviews. After hypothalamic damage (before setmelanotide), all participants described unrelenting hunger, drastically reduced energy or physical activity, and substantial weight gain negatively impacting self-esteem, emotions, and family dynamics. With setmelanotide, all participants reported reduced weight or body mass index, and 4 reported reduced hunger, which was accompanied by improved food-seeking behaviors, sleep (eg, not waking at night for food), self-confidence, and mood. Participants identified reduced hunger and weight and improved emotions or mood as the most important treatment benefits. Additional benefits were improved social engagement, physical activity, and school/work performance. All reported satisfaction and a desire to continue setmelanotide.
CONCLUSIONS: Patients experienced negative consequences of hypothalamic damage on hunger, weight, and energy that were alleviated by setmelanotide, resulting in broad benefits for patients and caregivers.
