An evaluation of setmelanotide injection for chronic weight management in adult and pediatric patients with obesity due to Bardet–Biedl syndrome

ABSTRACT

Introduction

Bardet–Biedl Syndrome (BBS) is a rare, multisystemic ciliopathy with an incidence of obesity of 89%. Mutations in genes encoding BBS proteins are linked to reduced leptin sensitivity of hypothalamic POMC neurons and reduced activation of the melanocortin-4 receptor (MC4R) pathway due to deficient α-MSH production by hypothalamic POMC neurons. The MC4R pathway is involved in controlling body weight and energy metabolism, and its disruption is linked to hyperphagia and obesity. Setmelanotide is an MC4R agonist that counteracts deficiencies in the MC4R pathway of individuals with BBS.

Areas covered

Data from clinical trials were reviewed along with information available from setmelanotide’s approval for treatment of obesity in people ages ≥6y with a clinical diagnosis of BBS.

Expert opinion

Setmelanotide is available as a daily injectable that can be used for amelioration of obesity in people with Bardet–Biedl syndrome. Its cost is substantial, which may limit its use, but among those who respond, setmelanotide can reduce body mass dramatically and potentially improve comorbid conditions associated with obesity. Setmelanotide treatment has generally tolerable side effects, primarily injection site reactions and nausea/vomiting that generally improve with continued use; almost all people using setmelanotide experience marked skin darkening due to off-target activation of cutaneous MC1R.

KEYWORDS:

• Obesity
• pharmacotherapy
• setmelanotide
• melanocortin agonist
• Bardet–Biedl syndrome

Declaration of interest

J. A. Yanovski reports grant support for clinical trials from Rhythm Pharmaceuticals, Inc. for use of setmelanotide in clinical trials including for Bardet–Biedl Syndrome. J. A. Yanovski also reports grant support for unrelated pharmacotherapy research from Soleno Therapeutics, Inc., Versanis Bio, and Hikma Pharmaceuticals, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper is supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, of the US National Institutes of Health, grant ZIAHD00641.