Rhythm Pharma Shares Patient Experiences of Hyperphagia in Hypothalamic Obesity at ENDO 2024

Rhythm Pharmaceuticals, Inc., a biopharmaceutical company specializing in rare neuroendocrine diseases, has unveiled significant findings from its Phase 2 trial examining setmelanotide therapy for hypothalamic obesity (HO). These insights were shared during the Endocrine Society Annual Meeting & Expo (ENDO 2024) held in Boston from June 1-4.

David Meeker, M.D., Chair, President, and CEO of Rhythm, emphasized the importance of these advancements, highlighting the extensive clinical research program aimed at addressing hyperphagia and severe obesity linked to melanocortin-4 receptor (MC4R) pathway diseases. Meeker noted that patient and caregiver feedback indicated notable improvements in quality of life, beyond just clinical outcomes and reductions in body mass index (BMI).

In a qualitative analysis led by Dr. Christian Roth from the Seattle Children’s Research Institute, participants with acquired hypothalamic obesity reported issues such as significant weight gain, unrelenting hunger, reduced energy, and disrupted sleep before receiving setmelanotide therapy. Following treatment, all participants experienced enhanced energy, a desire for increased physical activity, and improved sleep, with most also reporting reduced hunger and better eating behaviors.

Further insights were provided by Dr. Roth through an analysis involving 58 individuals with MC4R pathway diseases, including hypothalamic obesity, proopiomelanocortin (POMC) deficiency, leptin receptor (LEPR) deficiency, or Bardet-Biedl syndrome (BBS). After one year of setmelanotide treatment, 92% of those with hypothalamic obesity, 89% with POMC deficiency, 36% with LEPR deficiency, and 42% with BBS showed improvements in at least one obesity class. Although patients with LEPR deficiency and BBS began with more severe weight issues, they still displayed overall weight category improvements post-treatment.

Additionally, a preclinical study on RM-718, a selective MC4R agonist aimed at addressing obesity without causing MC1R-related hyperpigmentation, was presented by Danica Grujic, Ph.D., Senior Director at Rhythm Pharmaceuticals. This study in a rodent model of obesity and insulin resistance demonstrated that RM-718 was well-tolerated and led to stable reductions in weight and food intake, alongside improved insulin sensitivity.

ENDO 2024 also showcased three additional posters from Rhythm and its collaborators. Dr. Elif Oral from the University of Michigan presented findings from the DAYBREAK trial, which explored the efficacy of setmelanotide in individuals with various MC4R pathway variants. The trial indicated that at least one patient in each variant group achieved a reduction of at least 10% in BMI during the 16-week open-label run-in period. Setmelanotide was generally well-tolerated with no new safety concerns.

Dr. Roth also discussed the design of Rhythm’s Phase 1 trial of RM-718 in patients with obesity or hypothalamic obesity, while Caroline Huber, Director at Rhythm Pharmaceuticals, presented the design of the RESTORE study. This real-world study aims to assess the effectiveness of setmelanotide in managing hyperphagia and chronic weight issues in a clinical practice setting, offering a deeper understanding of patient outcomes.

Rhythm Pharmaceuticals continues its commitment to transforming the lives of those with rare neuroendocrine diseases, spearheaded by its lead product, IMCIVREE® (setmelanotide). This MC4R agonist is approved for chronic weight management in patients with specific genetic deficiencies and BBS, with regulatory endorsements from both the U.S. FDA and European health authorities. The company is also advancing other investigational MC4R agonists, including LB54640 and RM-718, and developing small molecules for congenital hyperinsulinism treatment.