New trial demonstrates effectiveness of Setmelanotide for rare early childhood obesity

A recent clinical trial has shown promising results for setmelanotide, a medication designed to treat obesity caused by rare genetic disorders in children as young as two years old.

Published in The Lancet, the phase 3 VENTURE trial evaluated the safety and efficacy of setmelanotide in managing obesity linked to melanocortin-4 receptor (MC4R) pathway deficiencies, including proopiomelanocortin (POMC) or leptin receptor (LEPR) deficiencies, and Bardet-Biedl syndrome (BBS).

The trial, conducted across six international sites, enrolled 12 children aged two to five years with confirmed genetic disorders leading to obesity and excessive hunger (hyperphagia). The children received daily subcutaneous injections of setmelanotide for one year, with doses adjusted based on weight.

Researchers found 83 per cent of participants achieved a significant reduction (≥0.2-point decrease) in BMI Z score, a standardised measure comparing BMI to age and sex norms and on average, participants experienced an 18 per cent reduction in BMI over the 52-week period.

Children with POMC or LEPR deficiencies saw the most dramatic results, with a 26 per cent mean BMI reduction, compared to a 10 per cent reduction in children with BBS.

Key findings also highlighted that 91 per cent of caregivers reported that their children were less hungry compared to the start of the trial, highlighting the potential of setmelanotide to address hyperphagia, a major challenge in these disorders.

Adverse events were mild or moderate, with common side effects including skin hyperpigmentation, mild injection site reactions, and upper respiratory infections.

This is the first study to demonstrate the potential of setmelanotide in children under six years of age, offering hope for families managing these rare, life-altering conditions. Early intervention could help mitigate the long-term health risks associated with severe obesity, such as type 2 diabetes and cardiovascular disease.

The findings underscore the need for further research to confirm these results and expand access to setmelanotide for younger populations. As an early intervention, the drug shows promise in reducing the physical and emotional burdens associated with genetic obesity syndromes, providing a new therapeutic pathway for affected children and their families.