Rhythm Pharmaceuticals, Inc. (NASDAQ: RYTM) has announced positive topline results from the pivotal phase 3 transcend trial evaluating setmelanotide, a melanocortin-4 receptor (MC4R) agonist, for the treatment of acquired hypothalamic obesity. The trial, which is believed to be the largest and longest placebo-controlled trial for this condition, demonstrated a statistically significant reduction in body mass index (BMI) with setmelanotide in both adult and pediatric patients compared to placebo.
The primary endpoint of the trial was met, with patients on setmelanotide therapy achieving a mean BMI reduction of -16.5% compared with a +3.3% change for patients on placebo at 52 weeks. Notably, a -19.8% placebo-adjusted difference in BMI reduction was observed, and 80% of patients on setmelanotide achieved a BMI reduction of 5% or greater at 52 weeks.
The trial also revealed that 83% of patients on setmelanotide therapy achieved a 5% or greater reduction in BMI for patients 18 or older, and a -1.4 placebo-adjusted mean change in the weekly average of the daily maximal hunger score for patients 12 years old or older was observed.
No new safety signals with setmelanotide were noted, and the most common treatment-emergent adverse events included nausea, vomiting, diarrhea, injection site reaction, skin hyperpigmentation, and headache.
Rhythm Pharmaceuticals is preparing to submit a supplemental new drug application to the FDA and a type II variation request to the European Medicines Agency in the third quarter of 2025. These planned submissions could potentially pave the way for setmelanotide to become the first approved therapy for patients with acquired hypothalamic obesity.
Rhythm estimates that there are 5,000 to 10,000 people living with hypothalamic obesity in the U.S., 5,000 to 8,000 people living with hypothalamic obesity in Japan, and 3,500 to 10,000 people living with hypothalamic obesity in the E.U.
As a result of these announcements, the company's shares have moved 16.7% on the market, and are now trading at a price of $54.81. Check out the company's full 8-K submission here.
