Rhythm Pharmaceuticals, Inc. (NASDAQ:RYTM), a global commercial-stage biopharmaceutical company focused on transforming the lives of patients living with rare neuroendocrine diseases, today announced that results from its pivotal Phase 3 TRANSCEND trial evaluating setmelanotide, a melanocortin-4 receptor (MC4R) agonist, in patients with acquired hypothalamic obesity have been published in The New England Journal of Medicine (NEJM).

The TRANSCEND study is the largest and longest placebo-controlled clinical trial ever conducted in patients with acquired hypothalamic obesity. The publication highlights robust improvements in weight and hunger achieved with setmelanotide therapy in adult and pediatric patients aged four years and older.

"Patients with acquired hypothalamic obesity and their families face an urgent need for effective treatment options," said Dr. Christian Roth, a pediatric endocrinologist and principal investigator of the Norcliffe Foundation Center for Integrative Brain Research at Seattle Children’s Research Institute, who served as the senior author and was instrumental in the trial’s planning. "The results of the TRANSCEND trial demonstrate meaningful and consistent reductions in body mass index as well as improvements in hunger. For patients and families who experience the accelerated and sustained weight gain associated with hypothalamic injury, these findings represent a potentially transformative therapeutic advancement."

In this 52-week, randomized, double blind, placebo-controlled Phase 3 study, the first 120 patients who reached 52 weeks on therapeutic regimen were evaluated as the primary analysis cohort. Patients treated with setmelanotide achieved:

  • -19.8% placebo-adjusted difference in body mass index (BMI) reduction (n=120);
  • Primary endpoint of mean BMI reduction of -16.5% from baseline for all patients on setmelanotide therapy (n=81) compared with +3.3% BMI change for patients on placebo (n=39) at 52 weeks (p<0.0001);
  • 80% of patients on setmelanotide achieved BMI reduction of 5% or greater at 52 weeks; and
  • Clinically meaningful improvements in hunger.



     

Setmelanotide was generally well tolerated. No new safety signals were observed, and adverse events leading to treatment discontinuation were comparable between treatment and placebo groups.