Johns Hopkins University, Baltimore, MD, USA.
Hepatology. 2013 Jun;57(6):2143-54. doi: 10.1002/hep.26276.
Faldaprevir (BI 201335) is a potent, hepatitis C virus (HCV) NS3/4A protease inhibitor with pharmacokinetic properties supportive of once-daily (QD) dosing. Four hundred and twenty-nine HCV genotype (GT)-1 treatment-naïve patients without cirrhosis were randomized 1:1:2:2 to receive 24 weeks of pegylated interferon alfa-2a and ribavirin (PegIFN/RBV) in combination with placebo, faldaprevir 120 mg QD with 3 days of PegIFN/RBV lead-in (LI), 240 mg QD with LI, or 240 mg QD without LI, followed by an additional 24 weeks of PegIFN/RBV. Patients in the 240 mg QD groups achieving maintained rapid virologic response (mRVR; viral load [VL] <25 IU/mL at week 4 and undetectable at weeks 8-20) were rerandomized to cease all treatment at week 24 or continue receiving PegIFN/RBV up to week 48. VL was measured by Roche TaqMan. Sustained virologic response (SVR) rates were 56%, 72%, 72%, and 84% in the placebo, faldaprevir 120 mg QD/LI, 240 mg QD/LI, and 240 mg QD groups. Ninety-two percent of mRVR patients treated with faldaprevir 240 mg QD achieved SVR, irrespective of PegIFN/RBV treatment duration. Eighty-two percent of GT-1a patients who received faldaprevir 240 mg QD achieved SVR versus 47% with placebo. Mild gastrointestinal disorders, jaundice resulting from isolated unconjugated hyperbilirubinemia, and rash or photosensitivity were more common in the active groups than with placebo. Discontinuations resulting from adverse events occurred in 4%, 11%, and 5% of patients treated with 120 mg QD/LI, 240 mg QD/LI, and 240 mg QD of faldaprevir versus 1% with placebo.
Faldaprevir QD with PegIFN/RBV achieved consistently high SVR rates with acceptable tolerability and safety at all dose levels. The 120 and 240 mg QD doses are currently undergoing phase 3 evaluation. (HEPATOLOGY 2013;57:2143-2154).
法地拉韦（BI 201335）是一种强效的丙型肝炎病毒（HCV）NS3/4A 蛋白酶抑制剂，具有支持每日一次（QD）给药的药代动力学特性。429 例无肝硬化的 HCV 基因型（GT）-1 初治患者按 1:1:2:2 的比例随机分组，接受聚乙二醇干扰素 alfa-2a 和利巴韦林（PegIFN/RBV）联合安慰剂、法地拉韦 120mg QD 加 3 天 PegIFN/RBV 导入（LI）、240mg QD 加 LI 或 240mg QD 不加 LI，共 24 周。在 240mg QD 组中达到持续病毒学应答（SVR；第 4 周时病毒载量[VL]＜25IU/mL，第 8-20 周时无法检测到）的患者随机在第 24 周停止所有治疗或继续接受 PegIFN/RBV 治疗至第 48 周。VL 通过罗氏 TaqMan 法测量。安慰剂、法地拉韦 120mg QD/LI、240mg QD/LI 和 240mg QD 组的持续病毒学应答（SVR）率分别为 56%、72%、72%和 84%。92%的法地拉韦 240mg QD 治疗的快速病毒学应答（mRVR）患者达到 SVR，无论 PegIFN/RBV 治疗持续时间如何。接受法地拉韦 240mg QD 治疗的 GT-1a 患者中有 82%达到 SVR，而安慰剂组为 47%。与安慰剂相比，在接受法地拉韦 240mg QD 的患者中，有 82%的 GT-1a 患者达到 SVR。与安慰剂组相比，法地拉韦治疗组更常见轻度胃肠道疾病、孤立性未结合高胆红素血症所致黄疸和皮疹或光敏性。接受法地拉韦 120mg QD/LI、240mg QD/LI 和 240mg QD 治疗的患者因不良反应而停药的发生率分别为 4%、11%和 5%，而安慰剂组为 1%。
法地拉韦 QD 联合 PegIFN/RBV 在所有剂量水平均具有一致的高 SVR 率，且耐受性和安全性可接受。120mg 和 240mg QD 剂量目前正在进行 3 期评估。（HEPATOLOGY 2013；57:2143-2154）。
