ESPE2024 Poster Category 1 Late Breaking 1 (10 abstracts)
Evaluating Setmelanotide Treatment for 12 Months in Pediatric Age Groups With Rare Melanocortin-4 Receptor Pathway–Related Obesity: Efficacy in Weight Reduction and Safety Outcomes
Peter Kühnen 1 , Erica L. T. van den Akker 2 , Ashley H. Shoemaker 3 , Uzoma Okorie 4 , Charles F. Verge 5 , Ilene Fennoy 6 , Megan M. Kelsey 7 , Andrea M. Haqq 8 , Christian L. Roth 9,10 , Jill C. Garrison 11 , Martin Wabitsch 12 , Sadaf Farooqi 13 & Jesús Argente 14,15
1Department of Pediatric Endocrinology and Diabetology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin und Humboldt-Universität zu Berlin, Berlin, Germany. 2Division of Pediatric Endocrinology, Department of Pediatrics, Sophia Children’s Hospital and Obesity Center CGG, Erasmus University Medical Center, Rotterdam, Netherlands. 3Ian Burr Division of Endocrinology and Diabetes, Vanderbilt University Medical Center, Nashville, USA. 4Marshfield Clinic Research Institute, Marshfield, USA. 5Sydney Children’s Hospital Randwick and Paediatrics, University of New South Wales, Sydney, Australia. 6Division of Pediatric Endocrinology, Diabetes, and Metabolism, Columbia University Irving Medical Center, New York, USA. 7Department of Pediatrics, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, USA. 8Division of Pediatric Endocrinology, University of Alberta, Edmonton, Canada. 9Seattle Children’s Research Institute, Seattle, USA. 10Division of Endocrinology, Department of Pediatrics, University of Washington, Seattle, USA. 11Rhythm Pharmaceuticals, Inc., Boston, USA. 12Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany. 13Wellcome-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, United Kingdom. 14Department 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 III, Madrid, Spain. 15IMDEA Food Institute, Madrid, Spain
Objectives: Hyperphagia and severe obesity may result from impaired melanocortin-4 receptor (MC4R) signaling due to rare biallelic variants in POMC or PCSK1 (proopiomelanocortin [POMC] deficiency) or LEPR (leptin receptor [LEPR] deficiency), Bardet-Biedl syndrome (BBS) or acquired hypothalamic obesity (HO). Previously, setmelanotide in patients aged 2-17 years was well tolerated and improved weight-related measures and hunger severity. Here, we report changes in weight-related and safety measures after 12 months of setmelanotide in pediatric patients by age groups (2-5, 6-11, and 12-17 years).
Methods: Patients aged 2-17 years from 5 index clinical trials and a long-term extension trial with on-treatment measurements at baseline and Month 12 were included. Changes in body mass index (BMI) Z score per World Health Organization methodology from index trial baseline after 12 months of setmelanotide were assessed. Safety was evaluated by adverse event (AE) frequency.
Results: A total of 50 pediatric patients were analyzed, including those with POMC (n = 9) or LEPR (n = 7) deficiencies, BBS (n = 21), or HO (n = 13); 45 patients had data at Month 12. Mean (standard deviation [SD]) BMI Z score was reduced across disease state and age groups (Table). The most frequent AEs (≥20%) were skin hyperpigmentation (36/50; 72%), injection site erythema (22/50; 44%), vomiting (22/50; 44%), nausea (20/50; 40%), and injection site pruritus (20/50; 40%). AE frequency and severity did not differ substantially by age group. There were no serious treatment-related AEs.
| BMI Z score, mean (SD), n | POMC | LEPR: | BBS | HO | |
| 2-5 years | −5.55 (1.17), n = 3 | −4.82 (2.03), n = 3 | −1.33 (1.10), n = 5 | ||
| – 6-11 years | −1.15 (0.58), n = 2 | – | −0.81 (0.35), n = 4 | −2.34 (0.87), n = 5 | |
| 12-17 years | −1.86 (0.77), n = 4 | −0.48 (0.32), n = 3 | −0.77 (0.57), n = 10 | −1.34 (0.9), n = 6 | |
| BMI, body mass index; SD, standard deviation. | |||||
Conclusion: Pediatric patients with obesity related to POMC or LEPR deficiencies, BBS, or HO had improvements in weight-related measures regardless of age group and obesity causes. The greater absolute reduction in BMI Z score among those ages 2-5 years across obesity causes may reflect overall higher baseline scores and may additionally highlight the importance of early intervention. More understanding is needed about response variation across obesity causes and analyzing the impact beyond changes in weight-related parameters alone (eg, hyperphagia and quality of life). These weight-related findings and the favorable tolerability across ages support setmelanotide use in developmental ages in approved indications of hypothalamic MC4R pathway disruptions.
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