Rhythm Gives Progress Report on Development of Setmelanotide for Genetic Obesity Disorders

Ana Pena, PhD avatar

by Ana Pena, PhD |

Share this article:

Share article via email
parent genetics

Rhythm Pharmaceuticals expects the first results of Phase 3 trials assessing its lead candidate setmelanotide for POMC and LEPR deficiency obesity in the third quarter of 2019.

The company also plans to apply for a new drug application to the U.S. Food and Drug Administration in late 2019 or early 2020.

Furthermore, it anticipates completing patient enrollment later this year for its recently launched pivotal Phase 3 trial (NCT03746522) evaluating setmelanotide as a therapy for Bardet-Biedl (BBS) and Alström syndrome, two other genetic obesity diseases, and predicts the announcement of topline data in 2020.

Throughout 2019, the company will also continue to enroll patients in its ongoing Phase 2 basket trial (NCT03013543) evaluating setmelanotide for the treatment of several rare genetic obesity disorders, including those affecting the melanocortin-4 receptor (MC4R) pathway.

Setmelanotide is a first-in-class activator of the MC4R pathway, an important signaling circuit in the brain that regulates weight by controlling the sensation of hunger or fullness, and the body’s energy consumption.

Variants in genes along the MC4R pathway are associated with persistent hunger, known as hyperphagia, and severe obesity starting early in life, including mutations in the genes POMC (pro-opiomelanocortin), PCSK1 (prohormone convertase 1), LEPR (leptin receptor), and MC4R.

Rhythm believes that setmelanotide could work as a replacement therapy to restore the lost activity of the MC4R pathway, recovering weight and appetite control in patients with rare genetic disorders affecting the pathway.

Earlier efficacy studies, namely data from the Phase 2 basket study, showed that setmalanotide was able to reduce excessive eating and body weight in patients with POMC and LEPR deficiencies, and with BBS.

Based on these positive results, an important part of the company’s pipeline concentrates on Phase 3 studies to confirm the efficacy and safety of the therapy in patients with these genetic obesity disorders.

“Our vision at Rhythm is to transform the care of obesity by delivering the first approved therapeutic for people living with rare genetic disorders of obesity due to impairments of the melanocortin-4 receptor (MC4R) pathway, and building an integrated community of patients, caregivers, healthcare providers, and payors to better address these conditions,” Keith Gottesdiener, MD, CEO of Rhythm, said in a press release.

“In 2018, we made important progress,” Gottesdiener added. “In addition to advancing setmelanotide into three pivotal trials, we shared new clinical data demonstrating setmelanotide’s ability to have dramatic impacts on weight and hunger in people with different MC4R pathway deficiencies.”

The company has also launched the TEMPO registry, a platform to gather critical information on the daily burden of rare genetic obesity disorders affecting the MC4R pathway.

Recent Posts