Nie Tina, Heo Young-A, Shirley Matt
Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
Drugs. 2023 Oct;83(15):1425-1432. doi: 10.1007/s40265-023-01943-z. Epub 2023 Sep 20.
Silencing the transthyretin (TTR) gene is an effective strategy in the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis. Vutrisiran (Amvuttra), an RNA interference (RNAi) therapeutic targeting TTR mRNA, is approved in the USA and EU for the treatment of adults with polyneuropathy of hATTR amyloidosis. N-acetylgalactosamine conjugation and enhanced stabilisation chemistry are utilised to target vutrisiran to the liver and increase stability, respectively, allowing for subcutaneous administration once every 3 months. In a pivotal phase 3 study in patients with hATTR amyloidosis with polyneuropathy, subcutaneous vutrisiran 25 mg every 3 months significantly reduced neuropathy impairment versus external placebo. Vutrisiran was also associated with significant improvements in neuropathy-specific quality of life, gait speed, nutritional status and disability scores. Vutrisiran was generally well tolerated; the only common adverse events to occur at a greater incidence than with external placebo were pain in extremity and arthralgia. Vutrisiran reduces serum vitamin A levels and vitamin A supplementation is recommended. In conclusion, vutrisiran is an efficacious and generally well-tolerated alternative option for the treatment of polyneuropathy of hATTR amyloidosis, which has the potential advantage of infrequent subcutaneous dosage.
沉默转甲状腺素蛋白（TTR）基因是治疗遗传性转甲状腺素蛋白介导的（hATTR）淀粉样变性的有效策略。Vutrisiran（Amvuttra）是一种靶向TTR mRNA的RNA干扰（RNAi）疗法，已在美国和欧盟获批用于治疗患有hATTR淀粉样变性多发性神经病的成人。N-乙酰半乳糖胺偶联和增强稳定性化学分别用于将vutrisiran靶向肝脏并提高稳定性，从而允许每3个月皮下给药一次。在一项针对患有hATTR淀粉样变性多发性神经病患者的关键3期研究中，每3个月皮下注射25 mg vutrisiran与外部安慰剂相比，显著降低了神经病变损害。Vutrisiran还与神经病变特异性生活质量、步态速度、营养状况和残疾评分的显著改善相关。Vutrisiran总体耐受性良好；唯一比外部安慰剂发生率更高的常见不良事件是肢体疼痛和关节痛。Vutrisiran会降低血清维生素A水平，建议补充维生素A。总之，Vutrisiran是治疗hATTR淀粉样变性多发性神经病的一种有效且总体耐受性良好的替代选择，具有皮下给药频率低的潜在优势。
