Setmelanotide

In two single-arm, open-label phase 3 trials, participants with obesity due to biallelic POMC/PCSK1 or LEPR deficiency received subcutaneous setmelanotide for approximately one year following a 12-week induction and a placebo-controlled withdrawal sequence. At about 1 year, 8 of 10 (80%) POMC-deficiency participants and 5 of 11 (45%) LEPR-deficiency participants achieved at least 10% weight loss. Mean most-hunger score fell by 27.1% (POMC; p=0.0005) and 43.7% (LEPR; p<0.0001). The most common adverse events were injection-site reactions, skin hyperpigmentation, and nausea, with no serious treatment-related events.

This study tested setmelanotide in people with two rare inherited forms of severe, early-onset obesity caused by faulty POMC or leptin-receptor (LEPR) genes. After about a year of daily injections, most patients lost substantial weight (10% or more) and reported far less intense hunger. Side effects were generally mild, mainly injection-site reactions, darkening of the skin, and nausea, supporting the drug's approval for these conditions.

This multicentre, randomised, double-blind, placebo-controlled phase 3 trial enrolled patients aged 6 years or older with Bardet-Biedl syndrome or Alström syndrome and obesity, randomised to setmelanotide or placebo for 14 weeks, followed by open-label setmelanotide through 52 weeks. The trial met its primary endpoint: a significantly greater proportion of setmelanotide-treated patients achieved at least 10% BMI reduction at 52 weeks versus placebo, alongside significant reductions in body weight and hunger scores. The most frequent adverse events were skin hyperpigmentation, injection-site reactions, and nausea, consistent with the drug's known safety profile.

This trial studied setmelanotide in people with Bardet-Biedl syndrome (and the related Alström syndrome), rare genetic disorders that cause relentless hunger and obesity. Patients who received the drug for about a year lost significantly more weight and felt less hungry than those on a placebo. Side effects were mostly mild, such as skin darkening, injection-site reactions, and nausea, and the results led to FDA approval for Bardet-Biedl syndrome.