FDA Approves Rhythm’s Drug for Rare Genetic Diseases of Obesity

The U.S. Food and Drug Administration granted approval to Rhythm Pharmaceuticals’ Imcivree for chronic weight management for people with certain rare genetic diseases of obesity, the first-ever FDA approved therapy for these conditions.

The approval for patients six years and older is for people with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency confirmed by genetic testing.

Imcivree targets the MC4 receptor pathway, a neural pathway responsible for regulating hunger, energy expenditure, and body weight. The genetic variants in people with these conditions impairs the MC4 receptor pathway and as a result they feel extreme, insatiable hunger and that causes early-onset, severe obesity. 

“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,” said David Meeker, chairman, president and CEO of Rhythm. “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.”

The FDA approval of Imcivree is based on results from the largest studies conducted to date in obesity due to POMC, PCSK1 or LEPR deficiency. In phase 3 clinical trials, 80 percent of patients with obesity due to POMC or PCSK1 deficiency achieved greater than ten percent weight loss and 45.5 percent of patients with obesity due to LEPR deficiency achieved greater than ten percent weight loss  after one year of treatment with Imcivree.

Imcivree was generally well-tolerated in both trials. The most common adverse events were injection site reaction, skin hyperpigmentation, and nausea. Warnings and precautions include disturbance in sexual arousal, depression and suicidal ideation, skin pigmentation and darkening of pre-existing nevi. There may be a risk of serious adverse reactions due to benzyl alcohol preservative in neonates and low birth weight infants. Imcivree is not approved for use in neonates or infants.

“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, pediatric endocrinologist at University of Florida Health. “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.”

Rhythm expects to make Imcivree commercially available to patients 6 years of age and older with obesity due to POMC, PCSK1 or LEPR deficiency in the United States in the first quarter of 2021.

The FDA issued a Rare Pediatric Disease Priority Review Voucher to Rhythm with the approval.  The PRV can be redeemed to receive priority review for any subsequent marketing application or sold or transferred to other companies for their programs. The FDA previously granted Breakthrough Therapy Designation to setmelanotide for the treatment of obesity associated with genetic defects upstream of the MC4 receptor pathway, as well as orphan drug designation for obesity due to POMC (including PCSK1) and LEPR deficiencies.

Rhythm’s application for approval to market the drug in Europe to treat people living with obesity due to POMC, PCSK1 or LEPR deficiency is currently under review by the European Medicines Agency. The EMA has previously granted PRIority MEdicines (PRIME) designation for setmelanotide for the treatment of obesity and the control of hunger associated with deficiency diseases of the MC4 receptor pathway.

The Company is currently evaluating the drug for reduction in hunger and body weight in a pivotal phase 3 trial in people living with Bardet-Biedl or Alström syndrome with topline data expected late in the fourth quarter of 2020 or early in the first quarter of 2021. Rhythm also continues to enroll patients in its phase 2 basket study designed to rapidly facilitate proof-of-concept in new indications.