Evaluating setmelanotide treatment for 12 months in patients aged 6 to 12 with rare melanocortin-4 receptor pathway-related diseases: reduction of weight parameters

Haqq Andrea M.; Waele Kathleen De; Allison Bahm; Lewis Alexander M.; Guojun Yuan; James Swain; Uzoma Okorie; Jesus Argente

doi:10.1530/endoabs.109.OC6.2

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Endocrine Abstracts (2025) 109 OC6.2 | DOI: 10.1530/endoabs.109.OC6.2

SFEBES2025 Oral Communications Metabolism, Obesity and Diabetes (6 abstracts)

Evaluating setmelanotide treatment for 12 months in patients aged 6 to 12 with rare melanocortin-4 receptor pathway–related diseases: reduction of weight parameters

Andrea M. Haqq ¹ , Kathleen De Waele ² , Allison Bahm ³ , Alexander M. Lewis ⁴ , Guojun Yuan ⁴ , James Swain ⁵ , Uzoma Okorie ⁶ & Jesús Argente ^7,8

Author affiliations

¹Division of Pediatric Endocrinology, University of Alberta, Alberta, Canada; ²Department of Pediatric and Adolescent Endocrinology, Ghent University Hospital, Ghent, Belgium; ³Peel Memorial Hospital, Totonto, Canada; ⁴Rhythm Pharmaceuticals, Inc., Boston, USA; ⁵HonorHealth Bariatric Center, Scottsdale, USA; ⁶Marshfield Clinic Research Institute, Marshfield, USA; 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 III, Madrid, Spain; ⁸IMDEA Food Institute, Madrid, Spain

Background: Impaired melanocortin-4 receptor (MC4R) signaling due to rare genetic defects such as biallelic variants in POMC or PCSK1 (leading to proopiomelanocortin [POMC] deficiency) or LEPR (leading to leptin receptor [LEPR] deficiency), or Bardet-Biedl syndrome (BBS) may result in hyperphagia and severe obesity. Previously, setmelanotide in patients aged 2-17 years was well tolerated and improved hunger severity and weight-related measures. Here, we report changes in weight measures after 12 months of setmelanotide in paediatric patients aged 6 to 12.

Methodology: Patients from index clinical trials with on-treatment measurements at Baseline and Month 12 were included. Changes in weight, body mass index (BMI) and BMI z-score per World Health Organization methodology from Baseline to 12 months of setmelanotide were assessed.

Results: A total of 11 paediatric patients were analyzed: 4 with POMC deficiency, and 7 with BBS. In both patient groups, mean (standard deviation [SD]) BMI z-score, BMI and weight were reduced at 52 weeks (Table). All 11 patients (100%) achieved a clinically significant reduction in BMI z-score from Baseline to Week 52 of at least 0.2 points. No new adverse events were reported.

Table 1. Change from Baseline to Week 52 in weight-related parameters by indication (absolute and percentage)
	BMI z-score	BMI (kg/m²)	Weight (kg)
POMC (n = 4)	−1.46 (0.60)	−6.68 (3.31)	−12.05 (7.17)
	−42.53% (17.78)	−20.52% (9.02)	−14.54% (8.30)
BBS (n = 7)	−0.99 (0.50)	–3.56 (2.08)	−3.87 (5.60)
	−28.24% (24.85)	–10.40% (7.64)	−4.59% (7.67)

Conclusions: Setmelanotide leads to clinically significant improvements in weight-related measures in paediatric patients aged 6 to 12 with obesity related to POMC deficiency or BBS. The therapeutic goal of weight stabilization in this age group is exceeded. These data support setmelanotide use in these ages in approved indications of hypothalamic MC4R pathway disruptions.