4-year setmelanotide weight outcomes of patients with POMC and LEPR deficiency obesity

Wendy Chung; James Swain; Peter Kuhnen; Martin Wabitsch; den Akker Erica van; Jill Garrison; Guojun Yuan; Jesus Argente; Karine Clement; Sadaf Farooqi

doi:10.1530/endoabs.99.EP5

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Endocrine Abstracts (2024) 99 EP5 | DOI: 10.1530/endoabs.99.EP5

ECE2024 Eposter Presentations Diabetes, Obesity, Metabolism and Nutrition (383 abstracts)

4-year setmelanotide weight outcomes of patients with POMC and LEPR deficiency obesity

Wendy Chung ¹ , James Swain ² , Peter Kühnen ³ , Martin Wabitsch ⁴ , Erica van den Akker ⁵ , Jill Garrison ⁶ , Guojun Yuan ⁶ , Jesús Argente ⁷ , Karine Clément ⁸ & Sadaf Farooqi ⁹

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¹Division of Molecular Genetics, Department of Pediatrics, Columbia University, New York, United States; ²Honor Health Research Institute, Scottsdale, United States; ³Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin und Humboldt-Universität zu Berlin, Institute for Experimental Pediatric Endocrinology, Berlin, Germany; ⁴Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany; ⁵Division of Pediatric Endocrinology, Department of Pediatrics, Sophia Children’s Hospital and Obesity Center CGG, Erasmus University Medical Center, Rotterdam, Netherlands; ⁶Rhythm Pharmaceuticals, Inc., Boston, United States; ⁷Department of Pediatrics and Pediatric Endocrinology, Universidad Autónoma de Madrid, University Hospital Niño Jesús, CIBER ‘Fisiopatología de la obesidad y nutrición’ (CIBEROBN), Instituto de Salud Carlos II; IMDEA Food Institute, Madrid, Spain; ⁸Assistance Publique Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital; Sorbonne University, Inserm, Nutrition and Obesity, Systemic Approaches (NutriOmique) Research Group, Paris, France; ⁹Wellcome-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, United Kingdom

Background: Patients with proopiomelanocortin (POMC; including variants in POMC or PCSK1) or leptin receptor (LEPR) deficiency due to biallelic gene variants have impaired melanocortin-4 receptor signaling that leads to hyperphagia and early-onset, severe obesity. Setmelanotide treatment in this population improved weight-related measures and hunger severity and was well tolerated. Reported here are long-term extension (LTE) outcomes after 4 years of setmelanotide treatment.

Methods: Patients with POMC or LEPR deficiency who achieved clinical benefit and acceptable safety in a prior trial of setmelanotide could enroll in the LTE (NTC03651765) and continue setmelanotide for ≥5 years or transition to a commercial product or other clinical trials. This analysis reports weight outcomes and adverse events at 4 years of setmelanotide treatment for patients who achieved a clinically meaningful, age-appropriate, 1-year index trial weight response defined as either ≥10% weight reduction (age ≥18 years at baseline) or reduction of ≥5 percentage points in percent of the 95th percentile for BMI (%BMI₉₅; age <18 years at baseline).

Results: A total of 24 patients entered the LTE with clinically meaningful weight response; 12 patients had 4 years of measurements and were included in this analysis. Of the 12 patients excluded, 3 pediatric patients transitioned to adulthood between the index trial and this analysis, 5 transitioned to commercial therapy, and 4 discontinued treatment. Compared with index trial baseline, the mean (SD) change in body weight was −32.6 kg (36.7) for patients aged ≥18 years (n=8) and −42.7 (22.44) percentage points in %BMI₉₅ for patients aged <18 years (n=4). No new safety signals were observed between the index trial and the LTE.

Conclusions: Continuous setmelanotide treatment in patients with POMC or LEPR deficiency is supported by sustained meaningful benefit in weight-related measures with no new safety signals at 4 years of treatment in this population.