Health Canada has approved Rhythm Pharmaceuticals’ IMCIVREE (setmelanotide solution for subcutaneous injection) for weight management in adult and paediatric patients 6 years of age and older with obesity due to Bardet-Biedl syndrome (BBS) or genetically-confirmed biallelic pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency due to variants interpreted as pathogenic, likely pathogenic, or of uncertain significance.
“We are pleased to announce Health Canada’s approval of IMCIVREE, marking a significant expansion of our footprint in North America and another important step forward in our efforts to deliver our precision medicine to people worldwide,” said Jennifer Chien, Executive Vice President, Head of North America for Rhythm. “We will leverage insights from our experience with launches in the US and Europe to support the strong team we have in Canada and look forward to making IMCIVREE commercially available in Canada in the months ahead.”
The early-onset obesity in patients with BBS and POMC, PCSK1 and LEPR deficiencies are caused by genetic variants that result in impairments in the melanocortin-4 receptor (MC4R) pathway, a system in the hypothalamus that regulates hunger, satiety, and energy expenditure. IMCIVREE is the first and only therapy approved in Canada for weight management in these patients following a Priority Review, which shortened the review process and was granted based on the serious nature of these conditions and lack of treatment options in Canada.
IMCIVREE is not indicated for patients with obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign, or other types of obesity not related to POMC, PCSK1 or LEPR deficiency, or BBS including obesity associated with other genetic syndromes and general (polygenic) obesity, as it would not be expected to be effective.
“Research has shown that the burden of severe obesity negatively affects the lives of patients and families,” said Professor Andrea M Haqq, Department of Pediatrics, Faculty of Medicine & Dentistry, University of Alberta. “Access to a therapy that addresses an underlying cause of their obesity is a significant advancement for patients and their families living with BBS and POMC, PCSK1 and LEPR deficiencies.”
The Health Canada approval is based on the results of the largest studies conducted to date in patients with obesity due to BBS as well as POMC, PCSK1, and LEPR deficiencies. In Phase 3 trials in each of these diseases, setmelanotide achieved statistically significant, clinically meaningful and sustained reductions of body weight, represented by at least a 10% weight loss from baseline at week 52. The trials met all primary endpoints and key secondary endpoints among patients at 52 weeks on therapy.
Results from these trials were featured in several publications, including the peer-reviewed journal The Lancet Diabetes and Endocrinology. In clinical trials, IMCIVREE was generally well-tolerated. Disturbance in sexual arousal, depression and suicidal ideation, increased skin pigmentation and darkening of pre-existing nevi, and benzyl alcohol toxicity in neonates and low birth-weight infants may occur. The most common adverse reactions were skin hyperpigmentation, injection site reactions and nausea.
“This approval will bring much-needed relief to patients and their families who need a therapeutic option that addresses an underlying cause of obesity associated with these rare MC4R pathway diseases,” said Dr Jill Hamilton, Pediatric Endocrinologist at The Hospital for Sick Children. “Setmelanotide has been shown to reduce the weight of patients living with BBS or POMC, PCSK1 or LEPR deficiency. The Health Canada approval will provide access to many patients in need, and I am excited to see the positive impact on these patients.”