PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2
PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2
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DOI：
10.1016/j.kint.2022.07.025
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发表时间：
2023-01-03
影响因子：
19.6
通讯作者：
Hoppe, Bernd
中科院分区：
文献类型：
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作者：
Baum, Michelle A.;Langman, Craig;Hoppe, Bernd
Nedosiran是一种研究性RNA干扰剂，旨在抑制肝乳酸脱氢酶的表达，该酶被认为负责草酸合成的终末步骤。草酸盐过量产生是原发性高草酸尿症（PH）所有遗传亚型的标志。在这项双盲、安慰剂对照研究中，我们将35名患有PH 1（n = 29）或PH 2（n = 6）且eGFR >= 30 mL/min/1.73 m（2）的参与者随机（2：1）分配至皮下注射奈多司兰或安慰剂，每月一次，持续6个月。24小时尿草酸盐（Uox）排泄量较基线降低百分比的曲线下面积（AUC）（主要终点），在第90-180天之间，与安慰剂相比，（最小二乘均值[SE]，D3507 [788] vs L1664 [1190];差异，5172; 95%CI 2929-7414; P < 0.001）。与安慰剂相比，接受奈多司兰的参与者中达到正常或接近正常的比例更高（
Nedosiran is an investigational RNA interference agent designed to inhibit expression of hepatic lactate dehydrogenase, the enzyme thought responsible for the terminal step of oxalate synthesis. Oxalate overproduction is the hallmark of all genetic subtypes of primary hyperoxaluria (PH). In this double-blind, placebo-controlled study, we randomly assigned (2:1) 35 participants with PH1 (n = 29) or PH2 (n = 6) with eGFR >= 30 mL/min/1.73 m(2) to subcutaneous nedosiran or placebo once monthly for 6 months. The area under the curve (AUC) of percent reduction from baseline in 24-hour urinary oxalate (Uox) excretion (primary endpoint), between day 90-180, was significantly greater with nedosiran vs placebo (least squares mean [SE], D3507 [788] vs L1664 [1190], respectively; difference, 5172; 95% CI 2929-7414; P < 0.001). A greater proportion of participants receiving nedosiran vs placebo achieved normal or near-normal (