Patients with hepatitis C virus (HCV) who have virological failure (VF) after treatment containing a nonstructural protein 5A (NS5A) inhibitor have limited retreatment options. MAGELLAN‐1 Part 2 was a randomized, open‐label, phase 3 study to evaluate the efficacy and safety of ribavirin (RBV)‐free glecaprevir and pibrentasvir (G/P; 300 mg/120 mg) in patients with chronic HCV and past VF on at least one NS3/4A protease and/or NS5A inhibitor‐containing therapy. Patients with compensated liver disease, with or without cirrhosis, and HCV genotype (GT) 1, 4, 5, or 6 were randomized 1:1 to receive 12 or 16 weeks of G/P. The primary endpoint was sustained virological response (SVR) at 12 weeks posttreatment (SVR12). Among 91 patients treated, 87 had GT1 and 4 had GT4 infection. SVR12 was achieved by 89% (39 of 44) and 91% (43 of 47) of patients who received 12 and 16 weeks of G/P, respectively. Virological relapse occurred in 9% (4 of 44) of patients treated with 12 weeks of G/P; there were no relapses with 16 weeks of treatment. Past treatment history with one class of inhibitor (protease or NS5A) had no impact on SVR12, whereas past treatment with both classes of inhibitors was associated with lower SVR12 rate. The most common adverse event (AE) was headache (≥10% of patients), and there were no serious AEs assessed as related to study drugs or AEs leading to discontinuation. Conclusion: Sixteen weeks of G/P treatment achieved a high SVR12 rate in patients with HCV GT1 infection and past failure to regimens containing either NS5A inhibitors or NS3 protease inhibitors. (Hepatology 2018;67:1253‐1260)

中文翻译：

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Glecaprevir/Pibrentasvir 用于治疗 HCV 基因型 1 或 4 且既往直接抗病毒治疗失败的患者


在接受非结构蛋白 5A (NS5A) 抑制剂治疗后出现病毒学失败 (VF) 的丙型肝炎病毒 (HCV) 患者的再治疗选择有限。 MAGELLAN-1 第 2 部分是一项随机、开放标签、3 期研究，旨在评估不含利巴韦林 (RBV) 的 glecaprevir 和 pibrentasvir（G/P；300 mg/120 mg）对慢性 HCV 患者和既往患者的疗效和安全性接受至少一种 NS3/4A 蛋白酶和/或 NS5A 抑制剂治疗的 VF。患有代偿性肝病、伴或不伴肝硬化以及 HCV 基因型 (GT) 1、4、5 或 6 的患者按 1:1 随机分配接受 12 或 16 周的 G/P。主要终点是治疗后 12 周的持续病毒学应答 (SVR) (SVR12)。在接受治疗的 91 名患者中，87 名 GT1 感染，4 名 GT4 感染。接受 12 周和 16 周 G/P 治疗的患者分别有 89%（44 名中的 39 名）和 91%（47 名中的 43 名）实现了 SVR12。接受 12 周 G/P 治疗的患者中有 9%（44 人中的 4 人）出现病毒学复发；治疗16周后未出现复发。过去使用一类抑制剂（蛋白酶或 NS5A）的治疗史对 SVR12 没有影响，而过去使用两类抑制剂的治疗与较低的 SVR12 率相关。最常见的不良事件 (AE) 是头痛（≥10% 的患者），并且没有评估与研究药物相关的严重 AE 或导致停药的 AE。结论：16 周的 G/P 治疗在 HCV GT1 感染且既往含有 NS5A 抑制剂或 NS3 蛋白酶抑制剂治疗方案失败的患者中实现了较高的 SVR12 率。 （肝病学 2018；67：1253‐1260）