Endocrine Abstracts

Background: Rare variants in the melanocortin-4 receptor (MC4R) pathway are associated with early-onset, severe obesity and hyperphagia. Setmelanotide, an MC4R agonist, reduced body mass index (BMI) and decreased hunger in patients with obesity due to biallelic variants in genes encoding proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) in Phase 3 trials. The current analysis assesses the durability of setmelanotide ef...

Background: Hypothalamic obesity (HO) is an acquired form of severe obesity that can occur following surgical resection of or radiotherapy for brain tumors and is often unresponsive to lifestyle modifications or traditional obesity pharmacotherapies. Here, we report weight- and body composition–related findings from a Phase 2 trial of setmelanotide, a melanocortin-4 receptor agonist, in patients with HO.Methods: A Phase 2, open-label, 16-week trial ...

Objective: Ideally, treatment strategies designed to reduce weight or body mass index in patients with obesity should reduce fat mass while preserving lean mass because reduced lean mass can negatively impact overall health and energy expenditure, thus favoring weight regain. In Phase 3 trials, 1 year of treatment with the melanocortin-4 receptor agonist setmelanotide led to weight reduction in patients with obesity due to biallelic variants in the genes encoding proopiomelano...

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 chemothera...

Background: In patients with Bardet-Biedl syndrome (BBS), signaling impairments in the melanocortin-4 receptor (MC4R) pathway lead to hyperphagia and severe obesity, which negatively impact quality of life (QOL). We evaluated the impact of setmelanotide, an MC4R agonist, on age-appropriate weight-related parameters, hunger, and QOL in a Phase 3 trial of patients with BBS to further characterize clinical benefit in this patient population.Methods: Patient...