Rhythm Pharmaceuticals, Inc. announced the first patient has been dosed with setmelanotide, the company's melanocortin-4 receptor (MC4R) agonist, in the Phase 2 DAYBREAK clinical trial to treat the severe obesity and hyperphagia potentially caused by a genetic variant that impairs function of the MC4R pathway. The company also announced the dosing of the first patient in the Phase 3 trial evaluating a switch from the daily to a novel weekly formulation of setmelanotide. The DAYBREAK trial [NCT04963231] is designed to evaluate setmelanotide in patients who carry a confirmed variant in one or more of 31 genes with strong or very strong relevance to the MC4R pathway, which regulates the body's energy balance, including appetite, energy expenditure and body weight.

Results from the DAYBREAK clinical trial have the potential to identify future patient populations and to inform the design of future registrational studies to support setmelanotide label expansion. DAYBREAK is a two-stage, double-blind, placebo-controlled trial that will be conducted at more than 75 trial sites across 12 countries. Rhythm plans to enroll approximately 500 patients (6 to 65 years old) with severe obesity and a variant in one of 31 genes relevant to the MC4R pathway.

Any patients who demonstrate a clinically meaningful response to setmelanotide at the end of a 16-week, open-label run-in period will be eligible to enter the second stage of the study. Stage 2 will be a 24-week, double-blind, placebo-controlled withdrawal study, in which patients will be stratified into genetically defined cohorts and randomized 2:1 to receive setmelanotide or placebo. The primary efficacy endpoint is a responder analysis based on the proportion of patients treated with setmelanotide who achieve a clinically meaningful weight reduction threshold at the end of treatment compared to patients treated with placebo.

Each genetically defined cohort can read out results independently.