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. 2020 Nov;22(11):2133-2140.
doi: 10.1111/dom.14133. Epub 2020 Jul 22.

Effect of setmelanotide, a melanocortin-4 receptor agonist, on obesity in Bardet-Biedl syndrome

Robert Haws  1 , Sheila Brady  2 , Elisabeth Davis  2 , Kristina Fletty  1 , Guojun Yuan  3 , Gregory Gordon  3 , Murray Stewart  3 , Jack Yanovski  2
Affiliations

Effect of setmelanotide, a melanocortin-4 receptor agonist, on obesity in Bardet-Biedl syndrome

Robert Haws et al. Diabetes Obes Metab. 2020 Nov.

Abstract

Aim: To report an analysis of ~1 year of setmelanotide treatment for obesity and hunger, as well as metabolic and cardiac outcomes, in individuals with Bardet-Biedl syndrome (BBS).

Materials and methods: Individuals aged 12 years and older with BBS received once-daily setmelanotide. The dose was titrated every 2 weeks to establish the individual therapeutic dose (≤3 mg); treatment continued for an additional 10 weeks. Participants who lost 5 kg or more (or ≥5% of body weight if <100 kg at baseline) continued into the 52-week extension phase. The primary outcome was mean percent change from baseline in body weight at 3 months. Hunger scores and safety were secondary outcomes.

Results: From February 2017 and February 2018, 10 individuals were screened; eight completed the 3-month treatment phase and seven completed the extension phase. Mean percent change in body weight from baseline to 3 months was -5.5% (90% CI, -9.3% to -1.6%; n = 8); change from baseline was -11.3% (90% CI, -15.5% to -7.0%; n = 8) at 6 months and -16.3% (90% CI, -19.9% to -12.8%; n = 7) at 12 months. All participants reported at least one treatment-emergent adverse event (AE), most commonly injection-site reaction. No AEs led to study withdrawal or death. Most, morning, and average hunger scores were reduced across time points.

Conclusions: Setmelanotide reduced body weight and hunger in individuals with BBS and had a safety profile consistent with previous reports. Setmelanotide may be a treatment option in individuals with BBS-associated obesity and hyperphagia.

Keywords: antiobesity drug, appetite control, obesity therapy, phase I-II study.

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Conflict of interest statement

RH is a consultant for Rhythm Pharmaceuticals, Inc., and Trinity Life Sciences. He receives grant funding from the Bardet‐Biedl Syndrome Foundation. JY receives grant support for clinical investigations from the NICHD, NIH, Soleno Pharmaceuticals Inc., and Rhythm Pharmaceuticals, Inc. GY, GG and MS are employed by and may own stock in Rhythm Pharmaceuticals, Inc. KF, ED and SB have no conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Participant enrolment and disposition. ITT, intent to treat
FIGURE 2
FIGURE 2
Mean weight and hunger changes with setmelanotide treatment in the per‐protocol population. (A) Mean change from baseline in body weight at each visit over 1 year of setmelanotide treatment. (B) Percent change from baseline in mean body weight over 1 year of setmelanotide treatment. (C) Mean change from baseline in most hunger score at each visit over 1 year of setmelanotide treatment. (D) Percent change in mean most hunger score over 1 year of setmelanotide treatment. (A) and (B): N = 8; (C) and (D): N = 5. Error bars are the 90% confidence interval. †Clinically meaningful change defined as weight loss of ≥5 kg (or ≥5% in patients with baseline body weight <100 kg). ‡n = 6
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