The Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) for Imcivree® (setmelanotide) for chronic weight management in patients 6 years of age and older with monogenic or syndromic obesity due to Bardet-Biedl syndrome.
Bardet-Biedl syndrome (BBS) is a rare genetic disorder that affects multiple organ systems, and includes symptoms such as obesity, hyperphagia, retinal degeneration, and reduced kidney function. Imcivree is a melanocortin 4 receptor (MC4R) agonist that re-establishes MC4 receptor pathway activity to reduce hunger and promote weight loss through decreased caloric intake and increased energy expenditure.
The approval was based on data from a phase 3 study (ClinicalTrials.gov Identifier: NCT03746522) that evaluated the efficacy and safety of Imcivree in patients 6 years of age and older with a clinical diagnosis of BBS and obesity (body mass index [BMI] of ≥30 kg/m2 for adults or weight ≥97th percentile for pediatric patients using growth chart assessments). Patients were randomly assigned to receive either Imcivree or placebo for 14 weeks, followed by an open-label treatment period in which all patients received Imcivree for 38 weeks.
Results showed the study met the primary and all key secondary endpoints with statistically significant reductions in weight and hunger at 52 weeks. In patients aged ≥6 years with obesity due to BBS (N=31), treatment with Imcivree was associated with a mean BMI reduction of 7.9% without requirements for diet and exercise. After 52 weeks, 61.3% of Imcivree-treated patients achieved at least a 5% loss in BMI and 38.7% achieved at least a 10% loss in BMI. Additionally, hunger scores (assessed by the Daily Hunger Questionnaire Item 2) decreased in Imcivree-treated patients during the 14-week placebo-controlled period and during the open-label treatment period.
The most common adverse reactions reported with Imcivree were injection site reactions, skin hyperpigmentation, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.
Imcivree is not recommended for use in patients with severe renal impairment and end stage renal disease. Patients should be advised that Imcivree may also cause spontaneous penile erections in males and sexual adverse reactions in females. Additionally, patients should be monitored for new onset or worsening of depression while taking Imcivree.
Imcivree is also indicated for chronic weight management in patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance.
The product is supplied as 10mg/mL solution of setmelanotide in 1mL multiple-dose vials. It is administered by subcutaneous injection.
- FDA approves treatment for weight management in patients with Bardet-Biedl Syndrome aged 6 or older. News release. US Food and Drug Administration. Accessed June 17, 2022. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-weight-management-patients-bardet-biedl-syndrome-aged-6-or-older
- Rhythm Pharmaceuticals announces FDA approval of Imcivree® (setmelanotide) for use in patients with Bardet-Biedl Syndrome. News release. Rhythm Pharmaceuticals, Inc. Accessed June 17, 2022. https://www.globenewswire.com/news-release/2022/06/16/2464337/0/en/Rhythm-Pharmaceuticals-Announces-FDA-Approval-of-IMCIVREE-setmelanotide-for-Use-in-Patients-with-Bardet-Biedl-Syndrome.html