Rare Daily Staff
The European Commission granted marketing authorization to Rhythm Pharmaceuticals’ Imcivree for the treatment of obesity and the control of hunger associated with the rare genetic conditions POMC, PCSK1, and LEPR deficiency in adults and children six years of age and above.
Imcivree is approved for the treatment of obesity and the control of hunger associated with genetically confirmed loss-of-function biallelic pro-opiomelanocortin (POMC), including PCSK1, deficiency or biallelic leptin receptor (LEPR) deficiency in adults and children 6 years of age and above.
Obesity due to POMC, PCSK1 or LEPR deficiency is an ultra-rare disease caused by variants in POMC, PCSK1 or LEPR genes that impair the MC4R pathway, which is a pathway in the hypothalamus that is responsible for regulating hunger, energy expenditure and consequently body weight. People living with obesity due to POMC, PCSK1 or LEPR deficiency struggle with extreme, insatiable hunger beginning at a young age, resulting in early-onset, severe obesity. As an MC4R agonist, Imcivree is designed to restore impaired MC4R pathway activity arising due to genetic deficits upstream of the MC4 receptor.
“With this authorization now in the EU, Imcivree becomes the first and only treatment option available to patients in EU countries and other territories including Northern Ireland to address the underlying cause of obesities driven by certain genetic defects in the melanocortin-4 (MC4) receptor pathway,” said David Meeker, chair, president and CEO of Rhythm. “This marks an important milestone for people in the EU member states living with POMC, PCSK1 or LEPR deficiency obesities, who now may have access to a therapy that has been shown to reduce hunger and body weight.”
The EC authorization of Imcivree (setmelanotide) is based on results from the largest studies conducted to date in obesity due to POMC, PCSK1 or LEPR deficiency. In two phase 3 clinical trials, 80 percent of ten patients with obesity due to POMC or PCSK1 deficiency achieved greater than ten percent body weight loss and 45.5 percent of 11 patients with obesity due to LEPR deficiency achieved greater than 10 percent body weight loss after one year of treatment with IMCIVREE. Additionally, in both studies, significant decreases in body mass index (BMI) were demonstrated across patients who were 6 to 17 years old at baseline (n=14).
In clinical trials, IMCIVREE was generally well-tolerated. 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.
“Rhythm’s phase 3 trials confirmed that treatment with IMCIVREE may deliver clinically meaningful impacts on obesity and severe hunger or hyperphagia. Many patients enrolled in these studies experienced weight loss of a magnitude that is unprecedented in the natural history of rare genetic diseases of obesity,” said Martin Wabitsch, professor of medicine and head of the Division of Pediatric Endocrinology and Diabetes at Ulm University Medical Center in Germany. “With this authorization, we are reminded of the importance of genetic testing, so that we can identify and properly diagnose patients with POMC, PCSK1 or LEPR deficiency obesity and offer eligible patients Imcivree, a pharmacological therapy designed to address the underlying cause of their disease.”
Imcivree is approved in the United States for chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to POMC, PCSK1, or LEPR deficiency. The condition must be confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance.
Photo: Martin Wabitsch, professor of medicine and head of the Division of Pediatric Endocrinology and Diabetes at Ulm University Medical Center in Germany