The US Food and Drug Administration (FDA) has approved setmelanotide (Imcivree, Rhythm Pharmaceuticals) for weight management in adults and children as young as 6 years with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing.
Individuals with these rare genetic causes of severe obesity have a normal weight at birth but develop persistent severe obesity within months due to insatiable hunger (hyperphagia).
Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for these disorders.
“Many patients and families who live with these diseases face an often burdensome stigma associated with severe obesity. To manage this obesity and control disruptive food-seeking behavior, caregivers often lock cabinets and refrigerators and significantly limit social activities,” said Jennifer Miller, MD, a pediatric endocrinologist at University of Florida Health, Gainesville, in a press release issued by the company.
“This FDA approval marks an important turning point, providing a much needed therapy and supporting the use of genetic testing to identify and properly diagnose patients with these rare genetic diseases of obesity,” she noted.
David Meeker, MD, chair, president, and chief executive officer of Rhythm Pharmaceuticals, added: “We are advancing a first-in-class, precision medicine that is designed to directly address the underlying cause of obesities driven by genetic deficits in the MC4R pathway.”
Setmelanotide was evaluated in two phase 3 clinical trials. In one trial, 80% of patients with obesity due to POMC or PCSK1 deficiency achieved greater than 10% weight loss after 1 year of treatment.
In the other trial, 45.5% of patients with obesity due to LEPR deficiency achieved greater than 10% weight loss with 1 year of treatment.
Setmelanotide was generally well-tolerated in both trials. The most common adverse events were injection site reactions, skin hyperpigmentation, and nausea.
The drug label notes that disturbances in sexual arousal, depression, and suicidal ideation, skin pigmentation, and darkening of pre-existing nevi may occur with setmelanotide treatment.
The drug label also notes a risk for serious adverse reactions due to benzyl alcohol preservative in neonates and low birth weight infants. Setmelanotide is not approved for use in neonates or infants.
The company expects the drug to be commercially available in the United States in the first quarter of 2021.
Setmelanotide for the treatment of obesity associated with rare genetic defects had FDA breakthrough therapy designation as well as orphan drug designation.
The company is also evaluating setmelanotide for reduction in hunger and body weight in a pivotal phase 3 trial in people living with Bardet-Biedl or Alström syndrome, and topline data are due soon.