ECEESPE2025 Poster Presentations MTEabolism, Nutrition and Obesity (125 abstracts)
Weight loss at 18 months of setmelanotide in 2-5-year-old patients with rare mc4r pathway diseases
Jesús Argente 1 , Charles Verge 2 , Uzoma Okorie 3 , Ilene Fennoy 4 , Megan Kelsey 5 , Casey Cokkinias 6 , Cecilia Scimia 6 , Guojun Yuan 6 & I. Sadaf Farooqi 7
1Department of Pediatrics & Pediatric Endocrinology, Universidad Autónoma de Madrid, University Hospital Niño Jesús, CIBER “Fisiopatología de la obesidad y nutrición” (CIBEROBN), Instituto de Salud Carlos III, IMDEA Institute, Madrid, Spain; 2Sydney Children’s Hospital Randwick and Paediatrics, University of New South Wales, Sydney, Australia; 3Marshfield Clinic Research Institute, Marshfield, United States; 4Division of Pediatric Endocrinology, Diabetes, and Metabolism, Columbia University Irving Medical Center, New York, United States; 5Department of Pediatrics, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, United States; 6Rhythm Pharmaceuticals, Inc, Boston, United States; 7Wellcome-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, United Kingdom
JOINT2565
Background: Rare variants in melanocortin-4 receptor (MC4R) pathway genes may impair MC4R signalling, leading to hyperphagia and early-onset, severe obesity. In a Phase 3, open-label trial, the MC4R agonist setmelanotide reduced weight and hunger in patients aged 2 to 5 years with proopiomelanocortin (POMC) deficiency, leptin receptor (LEPR) deficiency, or Bardet-Biedl syndrome (BBS) at 1 year (primary time point). Here, we report sustained improvements in weight outcomes at 18 months of setmelanotide.
Methods: The VENTURE trial (NCT04966741) evaluated 52 weeks of setmelanotide treatment in patients aged 2 to 5 years with hyperphagia and obesity due to biallelic POMC or LEPR variants or genetically confirmed BBS. This analysis assessed body mass index (BMI), BMI z-score, and percent of the BMI 95th percentile (%BMI95) from baseline to Month 18 of a long-term extension study.
Results: Eight patients (POMC/lEPR, n = 5; BBS, n = 3) completed 18 months of setmelanotide. All patients had severe obesity at baseline (BMI z-score range, 2. 4 to 7. 3) and had clinically meaningful reductions in weight at Month 18. The mean percent change from baseline in BMI was −21. 5% at Month 12, −22. 3% at Month 15, and −23. 3% at Month 18. The mean change from baseline in BMI z-score was −1. 9 at Month 12, −2. 0 at Month 15, and −2. 1 at Month 18. The mean change from baseline in %BMI95 in percentage points was −37. 0 at Month 12, −38. 5 at Month 15, and −41. 3 at Month 18. Skin hyperpigmentation (87. 5%; all treatment related) and nasopharyngitis (62. 5%; all not treatment related) were the most common reported adverse events.
Conclusion: In the first trial of setmelanotide in patients 2 to 5 years of age, robust reductions in age-appropriate weight measures were seen in all patients at 18 months of treatment, with no new safety concerns. No approved therapies for patients 2 to 5 years old with obesity in the studied populations currently exist, despite the need for early intervention with targeted therapy in these patients.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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