吉伏西兰:急性间歇性卟啉症的靶向治疗。

IF 2.9 3区 教育学 Q1 EDUCATION, SCIENTIFIC DISCIPLINES
Amy K Dickey, Rebecca K Leaf
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引用次数: 0

摘要

急性肝性卟啉症(AHPs)是一类罕见的遗传性疾病,与腹痛、呕吐、虚弱、神经病变和其他神经内脏症状有关。血红素合成的4种酶中有1种的致病性变异是AHP发展所必需的,而且急性发作的发生还需要诱导δ-氨基乙酰丙酸合成酶1 (ALAS1),这是肝脏血红素合成的第一步和限速步骤。Givosiran是一种RNA干扰药物,抑制肝脏ALAS1,设计用于治疗AHP。2019年,美国食品和药物管理局(fda)基于对94名AHP患者进行的3期临床试验的阳性结果批准了givosiran用于AHP,这些患者显示AHP发作明显改善,δ-氨基乙酰丙酸和卟啉胆色素原(AHP的主要疾病标志物)大幅下降。一项长期随访研究表明,AHP发作率、疾病生化指标和生活质量持续改善。现实世界的研究也证实了这些结果。常见的副作用包括注射部位反应、高同型半胱氨酸血症和肝肾生化异常。本文回顾了导致givosiran批准的研究,讨论了现实世界的临床数据,并强调了AHP治疗中仍存在的问题。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Givosiran: a targeted treatment for acute intermittent porphyria.

The acute hepatic porphyrias (AHPs) are a family of rare genetic diseases associated with attacks of abdominal pain, vomiting, weakness, neuropathy, and other neurovisceral symptoms. Pathogenic variants in 1 of 4 enzymes of heme synthesis are necessary for the development of AHP, and the onset of acute attacks also requires the induction of δ-aminolevulinic acid synthase 1 (ALAS1), the first and rate-limiting step of heme synthesis in the liver. Givosiran is an RNA interference medication that inhibits hepatic ALAS1 and was designed to treat AHP. In 2019 the US Food and Drug Administration approved givosiran for AHP based on positive results from a phase 3 clinical trial of 94 patients with AHP who demonstrated a marked improvement in AHP attacks and a substantial decrease in δ-aminolevulinic acid and porphobilinogen, the primary disease markers of AHP. A long-term follow-up study demonstrated continued improvement in AHP attack rates, biochemical measures of disease, and quality of life. Real-world studies have also confirmed these results. Common side effects include injection site reactions, hyperhomocysteinemia, and abnormalities of liver and renal biochemistries. This article reviews the studies that led to givosiran approval, discusses real-world clinical data, and highlights remaining questions in the treatment of AHP.

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来源期刊
Hematology. American Society of Hematology. Education Program
Hematology. American Society of Hematology. Education Program EDUCATION, SCIENTIFIC DISCIPLINES-HEMATOLOGY
CiteScore
4.70
自引率
3.30%
发文量
0
期刊介绍: Hematology, the ASH Education Program, is published annually by the American Society of Hematology (ASH) in one volume per year.
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