Endocrine Abstracts

Introduction: Rare genetic causes of obesity result from disruption of the melanocortin-4 receptor (MC4R) pathway, a regulator of energy balance. Patients with obesity due to variants in multiple genes, including POMC, LEPR, SRC1, and SH2B1, have shown weight and hunger reductions after treatment with setmelanotide, an MC4R agonist. DAYBREAK is a Phase 2 trial of setmelanotide in patients with additional gene variants with suggested relevance to the...

Background: Bardet-Biedl Syndrome (BBS) is a rare genetic disease in which impaired melanocortin-4 receptor (MC4R) signaling leads to hyperphagia and obesity. In an index Phase 3 trial, broad clinical benefit was observed in patients with BBS based on improvement or stabilization in ≥1 measure of weight, hunger, or quality of life with 1 year of treatment with the MC4R agonist setmelanotide. Reported here are long-term extension (LTE) weight outcomes after 3 years of set...

Background: Proopiomelanocortin (POMC; including biallelic variants in PCSK1) and leptin receptor (LEPR) deficiency are associated with hyperphagia and early-onset, severe obesity. Treatment with the melanocortin-4 receptor agonist setmelanotide for 1 year results in significant and sustained improvements in weight (POMC, −25.6%; LEPR, −12.5%), hunger, and quality of life. We used the metabolic syndrome Z score based on body mass index (MetS-Z-BMI) to asse...

Background: Patients with Bardet-Biedl syndrome (BBS), a rare syndrome associated with obesity and hyperphagia, commonly manifest traits of metabolic syndrome, including abdominal obesity, impaired fasting glucose, low high-density lipoprotein cholesterol, hypertriglyceridemia, and hypertension. Setmelanotide treatment results in significant improvement in weight, hunger, and quality of life in these patients and may improve measures associated with metabolic syndrome developm...

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...

Background: Patients with proopiomelanocortin (POMC; including variants in POMC or PCSK1) or leptin receptor (LEPR) deficiency due to biallelic gene variants have impaired melanocortin-4 receptor signaling that leads to hyperphagia and early-onset, severe obesity. Setmelanotide treatment in this population improved weight-related measures and hunger severity and was well tolerated. Reported here are long-term extension (LTE) outcomes after 4 years of setmelan...