New Treatment Shows Promising For Rare Obesity Disease

New Treatment Shows Promising For Rare Obesity Disease

Setmelanotide, a novel melanocortin 4 receptor (MC4R) agonist, may have beneficial effects on patients with pro-opiomelanocrotin (POMC) deficiency obesity, a rare genetic disorder that leads to early-onset obesity and abnormal unrelenting appetite, according to initial reports of a Phase 2 clinical trial.

The study, “Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist,” recently published in The New England Journal of Medicine, revealed that the compound can markedly induce weight loss and appetite reduction in POMC deficiency obesity patients.

The disease is estimated to effect between 100 and 500 patients worldwide, although only 50 patients have actually been reported. It is characterized by abnormal appetite in early infancy, which results in severe early-onset obesity. The condition is the result of genetic defects in the MC4R gene and currently has no approved treatment.

A Phase 2, non-randomized, open-label clinical trial evaluated the safety and efficacy of once-daily skin injection of setmelatonide in patients with the condition.


ith setmelanotide treatment, Patient 1 lost 112.4 lbs over 42 weeks, from a baseline weight of 341.7 lbs, and Patient 2 lost 45.2 lbs over 12 weeks, from a baseline weight of 336.9 lbs. Also, pre-study elevated insulin levels decreased substantially with setmelanotide treatment. Both patients continue in treatment.

Initial data from two patients, 21 and 26-years-old, revealed that the younger patient had a baseline weight of 341 lbs. and a reported weight loss of 112 lbs. upon 42 weeks of setmelanotide treatment. The 26-year-old patient lost 45 lbs. upon 12 weeks of setmelanotide treatment, from a baseline weight of 336 lbs. The weight loss was mainly due to the loss of body fat.

Both patients are still receiving treatment, but recent analysis showed a substantial decrease of pre-study elevated levels of insulin. Also, patients experienced substantial appetite loss, going from extreme hunger to no hunger over the course of treatment. The treatment was well tolerated; no serious adverse events were reported.

“These results provide further validation of the critical role of the MC4 pathway in weight regulation and the potential for setmelanotide to restore lost activity in this pathway by bypassing upstream defects of MC4R and by activating the MC4 pathway below such defects,” said Dr. Peter Kühnen, of the Institute for Experimental Pediatric Endocrinology, Charité Universitätsmedizin Berlin, Germany, lead investigator and lead author of the study, in a press release. “In this way, setmelanotide may serve as replacement therapy to reestablish weight and appetite control in patients with POMC deficiency and potentially other genetic disorders associated with obesity.”

The product is developed by Rhythm, a Boston based biopharmaceutical company that develops peptide therapeutics for rare genetic deficiencies that result in life-threatening metabolic disorders.

“We look forward to advancing the development program for setmelanotide and are grateful to our investigators and the participants in our clinical trial for their dedication and commitment to this important research effort,” said Keith Gottesdiener, Rhythm’s chief executive officer.

In addition to POMC deficiency, setmelanotide is currently in a Phase 2 clinical trial for the treatment of Prader-Willi Syndrome, another rare disorder likely caused by deficiencies in the MC4 pathway that results in obesity.

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