hrp0094p1-31 | Fat, Metabolism and Obesity A | ESPE2021

Efficacy and Safety of Setmelanotide in Individuals With Obesity Due to POMC or LEPR Deficiency: Phase 3 Results From Pivotal and Supplemental Cohorts

Farooqi Sadaf , Miller Jennifer , Ohayon Olga , Yuan Guojun , Scimia Cecilia , Stewart Murray , Yanovski Jack ,

Background: Disruption of the melanocortin-4 receptor pathway by genetic variants in POMC/PCSK1 or LEPR can result in hyperphagia and severe early-onset obesity. In the primary analyses of 2 pivotal Phase 3 trials, the melanocortin-4 receptor agonist setmelanotide was associated with significant reductions in body weight and hunger in patients with obesity due to proopiomelanocortin (POMC) or leptin receptor (LEPR) deficiency. These ...

hrp0094p2-222 | Fat, metabolism and obesity | ESPE2021

Design of a Phase 2, Double-Blind, Placebo-Controlled Trial of Setmelanotide in Patients With Genetic Variants in the Melanocortin-4 Receptor Pathway

Farooqi Sadaf , Wabitsch Martin , Chung Wendy , Ohayon Olga , Scimia Cecilia , Yuan Guojun , Shah Bhavik , Stewart Murray ,

Background: Rare genetic causes of obesity include variants in genes within the melanocortin-4 receptor (MC4R) pathway, a principal regulator of energy balance. Weight and hunger reductions following treatment with the MC4R agonist setmelanotide have been demonstrated in patients with obesity due to variants in multiple genes, including POMC, LEPR, SRC1, and SH2B1. We describe a trial design of setmelanotide in patients with addition...

hrp0094fc2.1 | Fat, Metabolism and Obesity | ESPE2021

Efficacy and Safety Results of a Phase 2 Trial of Setmelanotide in Obesity Due to SH2B1 Variants and 16p11.2 Deletion Syndrome

Argente Jesus , Farooqi Sadaf , Oral Elif , Goldstone Anthony , Ohayon Olga , Scimia Cecilia , Yuan Guojun , Stewart Murray , Chung Wendy ,

Background: Variants in SH2B1 or a 220–kilobase pair distal deletion of chromosome 16p11.2, including SH2B1, are associated with severe, early-onset obesity and hyperphagia. The melanocortin-4 receptor (MC4R) agonist setmelanotide is being investigated in individuals with rare variants in genes in the MC4R pathway.Methods: This ongoing, Phase 2 study (NCT03013543) enrolled individuals aged ≥6...

hrp0094fc2.3 | Fat, Metabolism and Obesity | ESPE2021

A Phase 2 Trial of the Melanocortin-4 Receptor Agonist Setmelanotide in Obesity Due to SRC1 Insufficiency: Body Weight, Body Mass Index Z Score, and Safety Results

Farooqi Sadaf , Argente Jesus , Martos-Moreno Gabriel , Oral Elif , Spiliotis Bessie , Kostopoulou Eirini , Pinhas-Hamiel Orit , Ben-Ami Michal , Ohayon Olga , Scimia Cecilia , Yuan Guojun , Stewart Murray , McCormack Shana ,

Background: Rare genetic diseases of obesity can be caused by genetic variants leading to disrupted activity of the melanocortin-4 receptor pathway (MC4R). Setmelanotide, an MC4R agonist, is being investigated in a basket study of populations with rare variants in different genes in the MC4R pathway who have early-onset, severe obesity and hyperphagia.Methods: This ongoing, Phase 2, open-label study (NCT03013543) enrolle...