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Drugs. 2021 Feb;81(3):397-403. doi: 10.1007/s40265-021-01470-9.
Setmelanotide (IMCIVREE™, Rhythm Pharmaceuticals) is a melanocortin-4 (MC4) receptor agonist developed for the treatment of obesity arising from proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency. The drug has received its first approval in the USA for chronic weight management in patients 6 years and older with obesity caused by POMC, PCSK1 and LEPR deficiency and has been granted PRIority MEdicines (PRIME) designation by the European Medicines Agency for the treatment of obesity and the control of hunger associated with deficiency disorders of the MC4 receptor pathway. Setmelanotide is also being developed in other rare genetic disorders associated with obesity including Bardet-Biedl Syndrome, Alström Syndrome, POMC and other MC4R pathway heterozygous deficiency obesities, and POMC epigenetic disorders. This article summarizes the milestones in the development of setmelanotide leading to this first approval for obesity caused by POMC, PCSK1 and LEPR deficiency.
司美格鲁肽（IMCIVREE™，Rhythm Pharmaceuticals）是一种黑色素皮质素 4（MC4）受体激动剂，用于治疗由前蛋白黑素细胞皮质素原（POMC）、蛋白水解酶枯草杆菌蛋白酶/kexin 型 1（PCSK1）或瘦素受体（LEPR）缺乏引起的肥胖症。该药物已在美国获得批准，用于治疗 6 岁及以上因 POMC、PCSK1 和 LEPR 缺乏引起的肥胖症患者的慢性体重管理，并已被欧洲药品管理局授予 PRIority MEdicines（PRIME）称号，用于治疗肥胖症和控制与 MC4 受体通路缺陷相关的饥饿。司美格鲁肽还在其他与肥胖相关的罕见遗传疾病中得到开发，包括 Bardet-Biedl 综合征、Alström 综合征、POMC 和其他 MC4R 通路杂合子缺乏性肥胖症以及 POMC 表观遗传疾病。本文总结了司美格鲁肽开发过程中的重要里程碑，这些里程碑导致了该药物在美国获得批准，用于治疗因 POMC、PCSK1 和 LEPR 缺乏引起的肥胖症。
