Rhythm Reports Durable Weight Loss with MC4R Drugs in Rare Obesity Disorders

Rare Daily Staff

Rhythm Pharmaceuticals reported new data showing that its melanocortin‑4 receptor (MC4R) drugs can drive sustained weight loss and ease extreme hunger in several rare forms of obesity, including acquired hypothalamic obesity, Bardet‑Biedl syndrome and Prader‑Willi syndrome.

Presenting in Chicago at the Endocrine Society’s Annual Meeting, Rhythm highlighted clinical and real‑world findings for setmelanotide and bivamelagon in acquired hypothalamic obesity (HO), Bardet‑Biedl syndrome (BBS) and Prader‑Willi syndrome (PWS). Rhythm CEO David Meeker said the data underscore how MC4R agonism can meaningfully reduce hyperphagia and improve weight‑related outcomes in patients with few or no effective treatment options.

The company said the findings strengthen the case for its approved injection setmelanotide and its oral experimental drug bivamelagon as options for people with severe, treatment‑resistant obesity linked to MC4R pathway defects.

In a phase 2 study with long‑term follow‑up, people with acquired hypothalamic obesity who received setmelanotide lost an average of 18.9 percent of their body mass index over two and a half years; the most common side effects were nausea, skin darkening, upper respiratory infections and vomiting. A separate phase 2 trial of once‑daily oral bivamelagon in twenty‑six patients with the same condition showed average BMI reductions of about seven percent to nearly seventeen percent after one year, along with lower hunger scores and similar gastrointestinal side effects.

Rhythm also reported phase 3 data in patients with acquired hypothalamic obesity who had previously undergone bariatric surgery but remained severely obese: three patients on setmelanotide saw BMI drops between 9.6 percent and 37.9 percent over one year, while one patient on placebo gained weight. In another phase 3 analysis, about seventy percent of children and adults on setmelanotide moved down at least one weight category after a year, and nearly forty‑four percent reached overweight or a healthy weight, compared with about fourteen percent on placebo.

Real‑world data in 286 people in the United States with obesity due to Bardet‑Biedl syndrome showed that sixty‑two percent of adults on setmelanotide lost at least ten percent of their body weight at twelve months, with fewer obesity‑related outpatient visits and worse starting weight and BMI in those who began treatment later. An interim analysis from the RESTORE study in twenty‑two people with Bardet‑Biedl syndrome found that most participants reported less constant hunger, fewer nighttime awakenings from hunger and reduced reliance on other anti‑obesity drugs after six months on setmelanotide, alongside lifestyle changes such as smaller portions and more exercise.

Rhythm said it recently shared six‑month phase 2 results of setmelanotide in Prader‑Willi syndrome and is running a broad development program across MC4R‑related diseases, including additional investigational agonists and a preclinical program in congenital hyperinsulinism, while continuing to market Imcivree for certain rare, genetically driven forms of obesity.

Photo: Rhythm CEO David Meeker