Novel MC4R agonist exhibits potential as new treatment for obesity, diabetes

Rhythm, a biotechnology company developing peptide therapeutics for metabolic diseases, today announced a study of obese primates treated with RM-493 showing a reversal of obesity and insulin resistance, and improvement in both heart rate and blood pressure. RM-493 is a novel peptide agonist targeting the melanocortin 4 receptor (MC4R) that is a clinical candidate for the treatment of obesity and diabetes. The study, "A Novel MC4R Agonist Reduces Body Weight and Improves Glucose Homeostasis in High Fat Diet-Induced Obese Rhesus Macaques," was presented at the 92nd annual meeting of the Endocrine Society (ENDO 2010) in San Diego.

"The goal of this study was to determine the effects of RM-493 on food intake, weight, and cardiovascular function, as well as to evaluate safety with long-term treatment," said Elizabeth Stoner, MD, Chief Development Officer of Rhythm. "The primates in this study were obese and prediabetic, caused by chronic consumption of a diet high in fats, and are an excellent model for metabolic syndrome in humans. Treatment with RM-493 resulted in impressive, persistent weight loss throughout the treatment period."

Twelve obese primates were treated with RM-493 for eight weeks at the OHSU Primate Center. The group demonstrated an average weight loss of 13%, predominantly due to the loss of body fat. Food intake was reduced only for a couple of weeks, yet the primates continued to lose weight throughout the eight-week treatment period. As they lost weight, the primates increased their physical activity and energy expenditure. There was a significant improvement in insulin sensitivity. And there were no signs of adverse behavioral effects such as nausea.

"This small peptide agonist of MC4R appears to shift the metabolic setpoint in these obese primates, reducing appetite and increasing energy expenditure with good tolerability," said Bart Henderson, President of Rhythm. "We are excited about this clinical candidate as a potential new treatment for obesity and diabetes."

SOURCE Rhythm Pharmaceuticals