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: Bardet–Biedl syndrome; Obesity; melanocortin agonist; pharmacotherapy; setmelanotide.