FDA Approves Setmelanotide For Obesity Caused by Genetic Deficiencies


The approval represents the first ever therapy for chronic weight management for obesity caused by a trio of genetic deficiencies.

The US Food and Drug Administration (FDA) has approved setmelanotide (IMCIVREE), the first-ever therapy for chronic weight management for patients with obesity caused by proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency.

The approval, awarded to Rhythm Pharmaceuticals, is indicated for chronic weight management in adult and pediatric patients at least 6 years old withPOMC, PCSK1, or LEPR deficiency confirmed by genetic testing.

“Our first new drug approval is a major milestone for Rhythm, and we look forward to delivering on the promise of IMCIVREE for patients suffering with obesity due to POMC, PCSK1 or LEPR deficiency,” David Meeker, MD, Chair, President and Chief Executive Officer of Rhythm, said in a statement. “With IMCIVREE, 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 melanocortin-4 (MC4) receptor pathway.”

Obesity caused by POMC, PCSK1, or LEPR is considered a rare disease that is often caused by POMC, PCSK1 or LEPR genes that impair the MC4 receptor pathway, which is a pathway in the hypothalamus that is responsible for regulating hunger, energy expenditure, and consequently body weight.

This patient population can struggle with extreme, insatiable hunger that often begins at a young age. This can result in early-onset severe obesity.

Setmelanotide is designed to restore impaired MC4 receptor pathway activity caused by genetic deficiencies upstream of the MC4 receptor.

The company has indicated plans to make the treatment available during the first quarter of 2021.

“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,” Jennifer Miller, MD, pediatric endocrinologist at University of Florida Health, said in a statement. “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.”

The approval is based on the results of a pair of phase 3 trials in which 80% of patients with obesity due to POMC or PCSK1 deficiency achieved greater than 10% weight loss and 45.5% of patients with obesity due to LEPR deficiency achieved greater than 10% weight loss after one year of treatment with the study drug.

Setmelanotide was generally well-tolerated in the clinical trials, with common adverse events including injection site reaction, skin hyperpigmentation, and nausea.

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