EP123: Design of a phase 2, double-blind, placebo-controlled trial of setmelanotide in patients with genetic variants in the melanocortin-4 receptor pathway

Abstract

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 the design of DAYBREAK, a Phase 2 trial of setmelanotide in patients with additional specific gene variants based on an evidence-based framework that suggested relevance to the MC4R pathway (ClinicalTrials.gov identifier: NCT04963231).