治疗进行性骨化性纤维发育不良的新药Palovarotene

Palovarotene:A new drug for fibrodysplasia ossificans progressive

进行性骨化性纤维发育不良(FOP)是一种罕见的遗传性、进行性结缔组织疾病,表现为在肌肉、关节、肌腱和韧带中发生异位骨化,导致患者主要关节强直、运动受限、畸形和严重残疾。2023年8月Palovarotene获美国食品药品监督管理局(FDA)批准用于减少进行性骨化性纤维发育不良成人和儿科患者(8岁及以上女童以及10岁及以上男童)的新发异位骨化容量,是目前唯一一款获批上市的治疗药物。该药为选择性维生素A酸受体γ(RAR-γ)激动药,通过抑制骨形态发生蛋白和SMAD1/5/8信号传导来减少异位骨化的发生。本文将对Palovarotene的药理作用、药代动力学及临床应用等方面进行介绍。

Progressive ossifying fibrous dysplasia(FOP) is a rare,hereditary,and progressive connective tissue disease characterized by heterotopic ossification(HO) formation in muscles,joints,tendons,and ligaments,leading to major joint stiffness,limited movement,deformity,and severe disability in patients.In August 2023,Palovarotene was approved by the US Food and Drug Administration(FDA) to reduce the formation of HO in adults and children aged 8 years and above for females and 10 years and above for males with FOP.It is currently the only approved curable drug worldwide.Palovarotene is a selective retinoic acid receptor γ(RAR-γ) agonist that reduces the formation of HO by inhibiting bone morphogenetic protein and SMAD 1/5/8 signaling.The pharmacological study,pharmacokinetics,clinical research,and safety are reviewed to comprehensively introduce Palovarotene.