Imcivree (setmelanotide) is an FDA-approved medication specifically designed to treat obesity and the control of hunger associated with genetic conditions affecting the melanocortin-4 receptor (MC4R) pathway. It targets certain genetic deficits that disrupt normal satiety signals, making it particularly effective for individuals with rare genetic disorders of obesity such as POMC, PCSK1, or LEPR deficiency. Imcivree is used under the guidance of healthcare providers to help manage weight in patients for whom other treatments have been ineffective.
Rare obesity syndromes associated with deficiencies in pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) are genetic conditions that result in severe early-onset obesity. These deficiencies disrupt critical pathways involved in appetite regulation and energy balance.
POMC Deficiency: This condition results from mutations in the POMC gene, which is essential for the production of several hormones, including ACTH, which stimulates cortisol production, and alpha-MSH, which regulates appetite. Individuals with POMC deficiency have severe obesity from an early age due to unregulated hunger and may also have adrenal insufficiency.
PCSK1 Deficiency: Mutations in the PCSK1 gene affect the enzyme responsible for processing several hormones, including insulin and those involved in appetite control. This deficiency leads to severe obesity, along with other endocrine disorders like diabetes, malabsorptive diarrhea, and hormonal imbalances.
LEPR Deficiency: This condition is caused by mutations in the LEPR gene, which codes for the leptin receptor. Leptin is a hormone crucial for regulating energy balance and suppressing appetite. LEPR deficiency results in severe, early-onset obesity due to the inability of the brain to respond to leptin signals, leading to uncontrolled hunger and food intake.
These genetic disorders are rare but highlight the significant role of these genes and hormones in maintaining normal body weight and energy homeostasis
The POMC/PCSK1/LEPR CDx Panel is a next generation sequencing (NGS)-based in vitro diagnostic test that analyzes genomic DNA isolated from blood or saliva. Specimens used with the test are K2EDTA blood collected using certain indicated K2EDTA blood collection devices and saliva collected using ORAcollect-Dx™ OCD 100 devices. The test detects germline nucleotide substitutions, short insertions and deletions, and copy number variants (CNVs) within the following 3 genes:
The test is a companion diagnostic device intended to select adult and pediatric patients 6 years of age and older who have obesity and certain variants in POMC, PCSK1, or LEPR genes for treatment with IMCIVREE® (setmelanotide) in accordance with the approved therapeutic product labeling. The POMC/PCSK1/LEPR CDx Panel is a single-site assay performed at PreventionGenetics, LLC (Marshfield, WI).
Whole blood and ORAcollect-Dx™ OCD-100 assisted saliva samples are collected and shipped to the PreventionGenetics laboratory.
IMCIVREE (setmelanotide) is indicated for the treatment of obesity and the control of hunger associated with rare genetic conditions such as POMC, PCSK1, and LEPR deficiencies. These genetic disorders lead to severe, early-onset obesity due to dysfunctional signaling pathways involved in appetite regulation.
IMCIVREE works by activating the melanocortin-4 receptor (MC4R), which plays a critical role in regulating hunger and energy expenditure. By stimulating this receptor, IMCIVREE helps to reduce appetite and promote weight loss in individuals with specific genetic mutations that disrupt normal MC4R signaling.
IMCIVREE is approved for use in adults and children aged 6 years and older who have been diagnosed with obesity due to POMC, PCSK1, or LEPR deficiencies confirmed by genetic testing. It is important for patients to undergo genetic testing to ensure they have the specific mutations targeted by IMCIVREE.
The most common side effects of IMCIVREE include injection site reactions, skin hyperpigmentation, nausea, headache, and diarrhea. Some patients may also experience mood changes and increased sexual arousal. It’s important to discuss potential side effects with your healthcare provider.
IMCIVREE is administered as a subcutaneous injection once daily. Patients or caregivers will be trained on how to properly inject the medication. It is important to follow the prescribed dosage and administration instructions provided by your healthcare provider to achieve the best results.
While taking IMCIVREE, patients are encouraged to maintain a healthy diet and engage in regular physical activity as recommended by their healthcare provider. These lifestyle changes can help maximize the benefits of the treatment and support overall health and well-being.
Rhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients and their families living with rare neuroendocrine diseases. Rhythm’s lead asset, IMCIVREE® (setmelanotide), an MC4R agonist designed to treat hyperphagia and severe obesity, is approved by the U.S. Food and Drug Administration (FDA) for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency confirmed by genetic testing, or patients with a clinical diagnosis of Bardet-Biedl syndrome (BBS). Both the European Commission (EC) and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) have authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 6 years of age and above. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases, as well as investigational MC4R agonists LB54640 and RM-718, and a preclinical suite of small molecules for the treatment of congenital hyperinsulinism. Rhythm’s headquarters is in Boston, MA.