Rhythm to Open Phase 2 Trial of Setmelanotide to People with 4 Other Genetic Obesity Disorders

Rhythm to Open Phase 2 Trial of Setmelanotide to People with 4 Other Genetic Obesity Disorders

Rhythm Pharmaceuticals is planning to expand its ongoing Phase 2 basket study investigating setmelanotide as an obesity treatment. The enlarged trial will include four additional genetic obesity disorders caused by an abnormal melanocortin-4 receptor (MC4R) pathway.

The announcement comes after genetic screening of nearly 14,000 patients with early onset, severe obesity suggested setmelanotide could also treat people with these disorders.

Genetic obesity is often caused by mutations in genes along the MC4R pathway, such as POMC (pro-opiomelanocortin), PCSK1 (prohormone convertase 1), LEPR (leptin receptor), and MC4R.

This pathway plays a vital role in controlling hunger and energy balance (how many calories we consume, and how many we burn). When disrupted, patients develop severe, early onset obesity and an excessively insatiable hunger, a condition called hyperphagia.

Rhythm’s trial (NCT03013543) is called a basket study because it is evaluating one therapy in various conditions linked to one pathway. It initially aimed to assess its MC4R pathway activator, setmelanotide, in people with POMC deficiencyLEPR deficiencyBardet-Biedl syndrome, and Alström syndrome — all obesity disorders linked to MC4R pathway.

With the expansion, the trial will also be open to people with SRC1 deficiency, SH2B1 deficiency, MC4R deficiency, and Smith-Magenis syndrome. It is currently enrolling at sites across the U.S. and in Europe; information is available here.

Patients will receive a setmelanotide injection once a day under the skin. Efficacy is primarily measured by the medication’s effect on weight loss. Other measures include its effect on hunger, body fat mass, and insulin sensitivity, as well as its possible side effects. The study runs for one year.

“Rhythm set out to transform the care for patients with rare genetic disorders of obesity based on our understanding of how the MC4R pathway regulates hunger and body weight,” Keith Gottesdiener, MD, the company’s chief executive officer, said in a press release.

In parallel with its setmelanotide studies, Rhythm is running a genetic screening program for obese children and adults with hyperphagia, hoping to identify additional genes involved in obesity. This may allow patients with other genetic disorders linked to obesity to be added to the setmelanotide trial in future expansions.

Genetic sequencing results will be shared at a company R&D event set for Sept. 25, starting at 8 a.m. ET. A live audio webcast will be available on the company’s website, and will remain posted for 30 days.

“In parallel with our ongoing efforts to progress setmelanotide through late-stage clinical trials, we have been working with our partners to sequence people living with early-onset, severe obesity to uncover more rare genetic disorders of obesity,” Gottesdiener said.

Rhythm is also conducting two Phase 3 trials exploring setmelanotide as an obesity treatment for patients with POMC and LEPR deficiency (NCT02896192 and NCT03287960). The company remains on track to announce top-line results from these trials at a medical conference this year.

“We look forward to providing additional detail on our patient identification and community building efforts, as well as our next indications for our expanded Basket trial,” Gottesdiener added.

“We are leveraging our strong scientific foundation to deliver setmelanotide as potentially the first approved therapeutic for MC4R pathway-driven disorders of obesity,” he concluded.

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.

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