Vutrisiran (previously ALN-TTRSC02) is a second-generation investigational RNAi therapeutic under development for the study of ATTR amyloidosis. Vutrisiran contains an siRNA that targets a sequence within the TTR mRNA which is conserved across wt and all known TTR variants. However, the Vutrisiran siRNA utilizes enhanced stabilization chemistry (ESC) and is conjugated to a triantennary GalNAc ligand, with the aim of enabling infrequent, subcutaneous (SC) dosing[1].

在非人灵长类动物中进行了药效动力学研究，以评估Vutrisiran的效力和持久性。给予不同剂量的单次皮下 (SC) 注射。1 mg/kg 的剂量实现了血清转甲状腺素蛋白 (TTR) 96% 的平均最大降低（最低点），且显著的抑制作用持续超过 4 个月。0.3 mg/kg 的较低剂量导致 55% 的降低。在独立的重复给药研究中，每月给予 1 或 3 mg/kg 将 TTR 降低维持在相对于基线的 96% 水平 [1]。