Setmelanotide May Help With Weight Loss in Patients With Obesity Due to Bardet-Biedl or Alström Syndrome

Shot of overweight woman eating an apple in her kitchen at home for weightloss.
This study was launched to analyze the effect of setmelanotide, a melanocortin 4 receptor agonist, on weight loss and hunger reduction in patients with obesity and a confirmed diagnosis of Bardet-Biedl syndrome (BBS) or Alströmsyndrome (AS).

The following article is part of our coverage of the Endocrine Society’s annual meeting (ENDO 2021) that is being held virtually from March 20-23, 2021. Endocrinology Advisor‘s staff will report on the top research in hormone science and clinical care. Check back for the latest news from ENDO 2021.


Setmelanotide, a melanocortin 4 receptor agonist, may help with weight loss in individuals with obesity due to Bardet-Biedl Syndrome (BBS) or Alström Syndrome (AS), according to results from a new Phase 3 study presented at ENDO 2021, the Endocrine Society’s annual meeting. This subcutaneous anti-obesity medication was able to lead to significant weight loss and hunger reduction, with responses being greater in individuals with BBS.

The researchers evaluated the effect of setmelanotide in terms of weight loss, hunger reduction, and safety outcomes in individuals (aged ≥6 years) with obesity and a genetically confirmed diagnosis of BBS or AS. Both of these conditions are believed to disrupt hypothalamic leptin-melanocortin signaling.

The study included 38 individuals with BBS (n=32) and AS (n=6), however 5 participants aged less than 12 years and 2 participants aged 12 years or older were not included in the primary analysis because they discontinued the trial before receiving any active therapy.

For this trial, obesity was defined as body mass index at or above 30 kg/m2 (in those aged ≥16 years) or weight greater than the 97th percentile (in those aged 6-15 years). The participants received setmelanotide or placebo for 14 weeks, followed by open-label setmelanotide.

All the participants received at least 12 months of drug. The study’ primary endpoint was the proportion of participants (≥12 years) who achieved 10% reduction in body weight or greater from baseline after 52 weeks of treatment.

For the primary endpoint, the statistical analysis calculated the binomial proportions calculated for each of the 100 multiple imputed data sets, which were combined using Rubin’s Rule to compare against the null hypothesis with 95% confidence intervals (CIs) and P values. The researchers conducted safety analyses in all participants. In participants aged 12 years and over, the researchers conducted efficacy analyses that included changes in body weight, body mass index Z score, and hunger from baseline.

The researchers found that 34.5% (95% CI, 17.5%-51.6%; P =0.0024) of participants achieved 10% reduction in body weight or more from baseline after about 52 weeks of treatment with setmelanotide. All of the responders had BBS, and the mean plus or minus SD percent change in body weight from baseline was −6.2% ± 8.6% (P <0.0001). The benefits of this agent were more pronounced in the younger participants. Those with BBS aged 17 years or younger (n=14) had a mean ± SD percent change in body mass index Z score from baseline was −24.5% ± 22.3%.

All the participants were asked to score their “most” hunger during the day. The study showed that the mean ± SD percent change in maximal daily hunger score from baseline was −30.8% ± 25.0% (P <0.0001). A total of 60.2% (95% CI, 35.3%-85.1%; P <0.0001) of the participants achieved a 25% or greater reduction in weekly average daily hunger score from baseline.

No significant adverse events (AEs) were reported in those receiving setmelanotide, and the most common AEs included skin hyperpigmentation (57.9%), injection site erythema (44.7%), or nausea (34.2%). There was 1 serious case of anaphylactic reaction, however, it occurred in a participant receiving placebo treatment.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Haws R, Clément K, Dollfus H, et al. A phase 3 trial in participants with obesity due to bardet-biedl syndrome or alström syndrome: efficacy and safety of the melanocortin 4 receptor agonist setmelanotide. Presented at ENDO 2021, the Endocrine Society’s annual meeting; March 20-23, 2021.