Efficacy and safety of setmelanotide in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

This multicentre phase 3 trial used a randomized, double-blind, placebo-controlled design to evaluate setmelanotide in 38 patients with Bardet-Biedl syndrome (BBS) or Alström syndrome — rare genetic conditions associated with severe obesity and chronic hyperphagia. The study included a 14-week double-blind phase followed by an open-label extension, totaling 52 weeks of follow-up.

Results demonstrated that 32.3% of adults with BBS achieved at least 10% body weight reduction by end of treatment. Weight loss was accompanied by significant reductions in hunger scores, measured by validated scales, representing a clinically meaningful benefit for patients whose hyperphagia is one of the most debilitating symptoms.

• During the double-blind phase, the setmelanotide group showed significantly greater weight reduction than placebo
• The most frequent adverse events included skin hyperpigmentation and injection site reactions
• The safety profile was consistent with previous setmelanotide studies

This study expanded the therapeutic indications of setmelanotide beyond POMC and LEPR deficiencies, demonstrating efficacy in genetic syndromes with distinct obesity mechanisms. The data contributed to regulatory approval of the drug for the treatment of obesity associated with Bardet-Biedl syndrome.