Valoctocogene Roxaparvovec基因治疗血友病。
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Ozelo MC, Mahlangu J, Pasi KJ Giermasz,莱维特广告,之际,M, Symington E, Quon DV,王JD, Peerlinck K,管西南,马丹B,关键NS,皮尔斯GF, B, O’mahony Kaczmarek R, Henshaw J, Lawal, Jayaram K,黄M,杨X,黄西王寅,金正日B
Valoctocogene Roxaparvovec基因治疗血友病。
郑传经地中海J。2022年3月17日,386 (11):1013 - 1025。doi: 10.1056 / NEJMoa2113708。
- PubMed ID
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35294811 (在PubMed]
- 文摘
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背景:Valoctocogene roxaparvovec (AAV5-hFVIII-SQ)是一种腺相关病毒5 (AAV5)的基因治疗载体含有凝血因子VIII互补DNA liver-selective启动子驱动的。以前治疗的有效性和安全性评估男性严重血友病一分之一1 - 2剂量递增阶段的研究。方法:我们进行了一次非盲、单一群体,多中心,第三阶段研究评估的有效性和安全性valoctocogene roxaparvovec严重血友病的男性,定义为一个第八因子1 IU /分升或更低的水平。参与者至少18岁,没有既存anti-AAV5抗体或VIII因子抑制剂的发展历史并曾接受预防与第八因子浓缩收到一个输液6 x10(13)向量的基因组valoctocogene roxaparvovec每公斤体重。主要终点是基线的变化因素八世活动(显色底物测定)在灌注后通过52周49。次要终点包括年度第八因子的变化集中使用和出血率。安全评估不良事件和实验室测试结果。结果:总体而言,134名参与者收到注入和完成超过51周的随访。在132年的人类免疫缺陷virus-negative参与者中,意味着VIII因子活动水平通过52周49已经增加了41.9 IU每分升(95%可信区间(CI), 34.1 - 49.7;P < 0.001; median change, 22.9 IU per deciliter; interquartile range, 10.9 to 61.3). Among the 112 participants enrolled from a prospective noninterventional study, the mean annualized rates of factor VIII concentrate use and treated bleeding after week 4 had decreased after infusion by 98.6% and 83.8%, respectively (P<0.001 for both comparisons). All the participants had at least one adverse event; 22 of 134 (16.4%) reported serious adverse events. Elevations in alanine aminotransferase levels occurred in 115 of 134 participants (85.8%) and were managed with immune suppressants. The other most common adverse events were headache (38.1%), nausea (37.3%), and elevations in aspartate aminotransferase levels (35.1%). No development of factor VIII inhibitors or thrombosis occurred in any of the participants. CONCLUSIONS: In patients with severe hemophilia A, valoctocogene roxaparvovec treatment provided endogenous factor VIII production and significantly reduced bleeding and factor VIII concentrate use relative to factor VIII prophylaxis. (Funded by BioMarin Pharmaceutical; GENEr8-1 ClinicalTrials.gov number, NCT03370913.).
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