Rhythm Pharmaceuticals has acquired the rights to develop and commercialize RM-853, an investigational therapy currently in preclinical research for Prader-Willi syndrome (PWS).
RM-853, formerly known as T-3525770, is a potent oral inhibitor of ghrelin o-acyltransferase (GOAT), the key enzyme involved in the body’s production of the active form of ghrelin, whose levels are increased in PWS. This increase results in an unrelenting feeling of hunger, known as hyperphagia, which leads to severe obesity.
In preclinical studies, RM-853 prevented body weight gain and reduced fat mass in mice fed a high-fat diet. The therapy also showed favorable pharmacokinetic, pharmacodynamic, and safety profiles.
After completing its preclinical research for RM-853, Rhythm plans to file, during the first quarter of 2020, an investigational new drug application with the U.S. Food and Drug Administration.
“The in-licensing of RM-853 represents an important milestone for Rhythm, as we execute on our mission of developing therapies for people living with rare genetic disorders of obesity,” Keith Gottesdiener, MD, chief executive officer of Rhythm, said in a press release.
“While PWS is one of the most prevalent rare genetic disorders of obesity, there are no approved treatments available. With RM-853, we have the opportunity to develop a first-in-class therapy with a likely dual mechanism of action, which may more effectively mediate the hyperphagia and weight gain associated with PWS,” Gottesdiener added.
Rhythm Pharmaceuticals also has completed a Phase 2 trial (NCT02311673) in PWS for one of its leading investigational therapies called setmelanotide, a melanocortin-4 receptor (MC4R) agonist. MC4R is part of a key biological pathway in humans that regulates weight by increasing the use of energy and reducing appetite.
Results showed that setmelanotide had a modest effect on reducing hyperphagia and led to clinically meaningful weight loss, but only in patients treated with the highest dose and for the longest period of time.
Rhythm plans to continue investigating the effects of setmelanotide in PWS parallel to the development of RM-853, and potentially testing the effects of both therapies combined.
“Rhythm aims to develop meaningful drug candidates for people living with metabolic disorders,” said Lex H.T. Van der Ploeg, PhD, chief scientific officer of Rhythm. “Our team has a deep understanding of the complex pathways involved in regulating bodyweight and appetite and is experienced in working with specialized endocrinologists and physicians to design and execute clinical trials that evaluate therapeutic options for people living with PWS.”
The new agreement gives full rights to Rhythm Pharmaceuticals for the development and commercialization of RM-853, formerly developed and commercialized by Takeda Pharmaceuticals. Takeda will receive an upfront payment of $5 million under the agreement plus royalties on future RM-853 sales.