Rhythm Pharmaceuticals, Inc. announced that Great Britain’s Medicines & Healthcare Products Regulatory Agency (MHRA) has granted marketing authorisation to IMCIVREE® (setmelanotide) for the treatment of obesity and the control of hunger associated with genetically confirmed loss-of-function biallelic pro-opiomelanocortin (POMC), including proprotein convertase subtilisin/kexin type 1 (PCSK1), deficiency or biallelic leptin receptor (LEPR) deficiency in adults and children 6 years of age and above. IMCIVREE was selected for evaluation as a “Highly Specialised Technology” by the National Institute for Health and Care Excellence (NICE). NICE is scheduled to review the dossier for IMCIVREE in December 2021. Guidance for coverage of IMCIVREE under the United Kingdom’s National Health Service (NHS) is anticipated in the second quarter of 2022. 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. The MHRA authorisation of IMCIVREE 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, 8 of 10 patients with obesity due to POMC or PCSK1 deficiency achieved greater than 10% body weight loss after one year of treatment with IMCIVREE and 5 of 11 patients with obesity due to LEPR deficiency achieved greater than 10% 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, nausea, and headache. Warnings and precautions include skin monitoring, heart rate and blood pressure monitoring, prolonged penile erection, and depression. In Great Britain, IMCIVREE is indicated 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. In the EU, IMCIVREE is indicated 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. IMCIVREE should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology. IMCIVREE should be prescribed and supervised by physicians with expertise in obesity with underlying genetic aetiology. WARNINGS AND PRECAUTIONS: Skin Monitoring: Setmelanotide may lead to generalised increased skin pigmentation and darkening of pre-existing naevi because of its pharmacologic effect. Full body skin examinations should be conducted annually to monitor pre-existing and new skin pigmentary lesions before and during treatment with setmelanotide. Heart rate and blood pressure monitoring: Heart rate and blood pressure should be monitored as part of standard clinical practice at each medical visit (at least every 6 months) for patients treated with setmelanotide. Prolonged penile erection: Spontaneous penile erections have been reported in clinical trials with setmelanotide. Patients who have a penile erection lasting longer than 4 hours should be instructed to seek emergency medical attention for potential treatment of priapism. Depression: In clinical trials, depression has been reported in patients treated with setmelanotide. Patients with depression should be monitored at each medical visit during treatment with IMCIVREE. Consideration should be given to discontinuing IMCIVREE if patients experience suicidal thoughts or behaviours. Paediatric Population: The prescribing physician should periodically assess response to setmelanotide therapy. In growing children, the impact of weight loss on growth and maturation should be evaluated. The prescribing physician should monitor growth (height and weight) using age- and sex-appropriate growth curves. Excipients: This medicinal product contains 10 mg benzyl alcohol in each ml. Benzyl alcohol may cause allergic reactions. Patients who are pregnant or breastfeeding should be advised of the potential risk from the excipient benzyl alcohol, which might accumulate over time and cause metabolic acidosis. This medicinal product should be used with caution in patients with hepatic or renal impairment, because of the potential risk from the excipient benzyl alcohol which might accumulate over time and cause metabolic acidosis. The most frequent adverse reactions are hyperpigmentation (51%), injection site reaction (39%), nausea (33%), and headache (26%).