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Rhythm submits Setmelanotide to FDA for rare genetic disorders of obesity

Wed, 04/01/2020 - 06:33
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Setmelanotide - Rhythm estimates there are approximately 100 to 500 patients in the US with POMC deficiency obesity and approximately 500 to 2,000 patients in the US with LEPR deficiency obesity

Rhythm Pharmaceuticals has completed its rolling submission of a New Drug Application (NDA) to the FDA for setmelanotide for the treatment of pro-opiomelanocortin (POMC) deficiency obesity and leptin receptor (LEPR) deficiency obesity.

Setmelanotide is an investigational, potent melanocortin-4 receptor (MC4R) agonist. The MC4R is part of the key biological pathway that independently regulates energy expenditure and appetite. Variants in genes may impair the function of the MC4R pathway, potentially leading to insatiable hunger and early-onset, severe obesity. Rhythm is currently developing setmelanotide as a targeted therapy to restore the function of an impaired MC4R pathway and, in so doing, reduce hunger and weight in patients with rare genetic disorders of obesity. Currently, no pharmacologic therapies exist to treat these conditions.

“The completion of our first NDA submission marks an integral first step in our journey to transform the care of people living with not only POMC and LEPR deficiency obesities, but also many other rare genetic disorders of obesity,” said Dr Murray Stewart, Chief Medical Officer of Rhythm Pharmaceuticals. “We look forward to further discussions with the FDA as we seek to obtain approval for setmelanotide, which we believe has the potential to address the insatiable hunger and early-onset, severe obesity that affects people living with POMC and LEPR deficiency obesities, who cannot be treated with lifestyle modifications alone and have no other treatment options.”

The FDA typically has a 60-day filing review period to determine whether the NDA is sufficiently complete and acceptable for filing. Rhythm has requested priority review for the application which, if granted, could provide a target FDA review period of six-months from the application filing date.  

Reported in August 2019, Rhythm’s Phase 3 clinical trials of setmelanotide in patients with POMC deficiency obesity and LEPR deficiency obesity met their primary endpoints and all key secondary endpoints, demonstrating a statistically significant and clinically meaningful reduction in weight loss and reduction in hunger after one year of treatment with setmelanotide. Over the course of the Phase 3 trials, for patients with POMC deficiency obesity, mean weight loss was 31.9kg or 70.2lbs, and for patients with LEPR deficiency obesity mean weight loss was 16.kg or 36.lbs.

POMC and LEPR deficiency obesities are ultra-rare disorders. Rhythm estimates there are approximately 100 to 500 patients in the US with POMC deficiency obesity and approximately 500 to 2,000 patients in the US with LEPR deficiency obesity. POMC deficiency obesity is a disorder caused by variants in the POMC or PCSK1 genes that can often lead to severe obesity beginning early in life and insatiable hunger, in addition to endocrine abnormalities, and sometimes red hair and light skin pigmentation. LEPR deficiency obesity is a disorder caused by variants in the LEPR gene that can often lead to severe obesity beginning early in life and insatiable hunger, in addition to endocrine abnormalities.

Most patients with POMC and LEPR deficiency obesity experience exponential weight gain in the first months of life, which continues rapidly over the course of their lives. This weight gain cannot be mitigated by diet, exercise or other lifestyle changes, or by existing therapeutic interventions.