MC4R agonist for obesity in young children scores high in phase III trial

The melanocortin-4 receptor (MC4R) agonist setmelanotide demonstrates efficacy in the management of obesity in children younger than 6 years, according to the results of a phase III trial.

The trial included 12 patients between 2 and 5 years of age (mean age 3.6 years, 58 percent male) who had hyperphagia and obesity due to proopiomelanocortin (POMC) or leptin receptor (LEPR) deficiency (n=7) or Bardet-Biedl syndrome (BBS) (n=5). All patients received open-label treatment with setmelanotide administered subcutaneously once daily for 52 weeks, starting at a dose of 0.5 mg then increasing every 2 weeks in 0.5 mg increments until reaching the maximum dose based on weight.

The coprimary endpoints were the percentage of patients reaching at least a 0.2-point decrease in BMI Z score and mean percent change in BMI at week 52. Other endpoints assessed were safety, hunger, weight-related outcomes, and caregiver burden.

At week 52, 10 patients (83 percent) achieved at least a 0.2-point reduction in BMI Z score per WHO methodology. The mean percent change in BMI from baseline was −18 percent in the overall population, −26 percent among those with POMC or LEPR deficiency, and −10 percent among those with BBS.

Mean reductions of 3.4 in BMI Z score and of 32.5 percent of the BMI 95th percentile were also observed at week 52. Most of the caregivers (91 percent) reported that patients were less hungry than at baseline.

The most common adverse events were skin hyperpigmentation, vomiting, nasopharyngitis, upper respiratory tract infection, and injection site reactions, all of which were either mild or moderate in intensity. None of the patients had serious adverse events or adverse events leading to study discontinuation or death.

The findings highlight the potential of setmelanotide as an early intervention to manage obesity in young children.