Rhythm Pharmaceuticals says Phase 3 TRANSCEND trial meets primary endpoint

Rhythm Pharmaceuticals (RYTM) announced topline results from the pivotal Phase 3 TRANSCEND trial evaluating setmelanotide, a melanocortin-4 receptor agonist, for the treatment of acquired hypothalamic obesity. The global trial met its primary endpoint with a statistically significant and highly clinically meaningful reduction in body mass index with setmelanotide in both adult and pediatric patients versus placebo. Highlights from the topline data include: -19.8% placebo-adjusted difference in BMI reduction; Primary endpoint of mean BMI reduction of -16.5% from baseline for all patients on setmelanotide therapy compared with +3.3% BMI change for patients on placebo at 52 weeks; and 80% of patients on setmelanotide achieved BMI reduction of 5% or greater at 52 weeks. The global Phase 3 TRANSCEND trial is believed to be the largest and longest placebo-controlled trial to evaluate a therapy for patients with acquired hypothalamic obesity. The double-blinded, 52-week trial enrolled 120 patients, randomized 2:1. In addition to the primary endpoint and other data points above, clinically meaningful improvements were observed across key secondary endpoints at week 52, including: 83% percent of patients on setmelanotide therapy achieved 5% or greater reduction in BMI or BMI Z-score reduction of 0.2 or greater points; and -1.4 placebo-adjusted mean change in weekly average of the daily maximal hunger score for patients 12 years old or older. No new safety signals with setmelanotide were observed, in line with setmelanotide’s well-established and well-understood safety profile. Consistent with prior clinical experience, setmelanotide was generally well tolerated in the TRANSCEND study. The most common treatment-emergent adverse events were nausea, vomiting, diarrhea, injection site reaction, skin hyperpigmentation and headache. No serious adverse events leading to study discontinuation were reported.