Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainsville, USA.
Ann Hepatol. 2012 Jan-Feb;11(1):15-31.
Balapiravir (R1626, RG1626) is the prodrug of a nucleoside analogue inhibitor of the hepatitis C virus (HCV) RNA-dependent RNA polymerase (R1479, RG1479). This phase 2, double-blind international trial evaluated the optimal treatment regimen of balapiravir plus peginterferon alfa-2a (40KD)/ribavirin.
Treatment-naive genotype 1 patients (N = 516) were randomized to one of seven treatment groups in which they received balapiravir 500, 1,000, or 1,500 mg twice daily, peginterferon alfa-2a (40KD) 180 or 90 µg/week and ribavirin 1,000/1,200 mg/day or peginterferon alfa-2a (40KD)/ribavirin. The planned treatment duration with balapiravir was reduced from 24 to 12 weeks due to safety concerns.
The percentage of patients with undetectable HCV RNA was consistently higher in all balapiravir groups from week 2 to 12. However, high rates of dose modifications and discontinuations of one/all study drugs compromised the efficacy assessment and resulted in similar sustained virological response rates in the balapiravir groups (range 32-50%) and the peginterferon alfa-2a (40KD)/ribavirin group (43%). Balapiravir was discontinued for safety reasons in 28-36% of patients (most often for lymphopenia) and the percentage of patients with serious adverse events (especially hematological, infection, ocular events) was dose related. Serious hematological adverse events (particularly neutropenia, lymphopenia) were more common in balapiravir recipients. Two deaths in the balapiravir/peginterferon alfa-2a/ribavirin combination groups were considered possibly related to study medication.
Further development of balapiravir for the treatment of chronic hepatitis C has been halted because of the unacceptable benefit to risk ratio revealed in this study (www.ClinicalTrials.gov NCT 00517439).
拉替拉韦（R1626，RG1626）是一种核苷类似物，可抑制丙型肝炎病毒（HCV）的 RNA 依赖性 RNA 聚合酶（R1479，RG1479）。这是一项 2 期、双盲国际试验，评估了拉替拉韦联合聚乙二醇干扰素 alfa-2a（40KD）/利巴韦林的最佳治疗方案。
治疗初治的基因型 1 患者（N=516）被随机分配到 7 个治疗组中的一个，接受拉替拉韦 500、1000 或 1500mg，每日 2 次，聚乙二醇干扰素 alfa-2a（40KD）180 或 90μg/周和利巴韦林 1000/1200mg/天或聚乙二醇干扰素 alfa-2a（40KD）/利巴韦林。由于安全性问题，计划的拉替拉韦治疗时间从 24 周缩短至 12 周。
从第 2 周到 12 周，所有拉替拉韦组的 HCV RNA 不可检测率始终较高。然而，高剂量调整率和所有研究药物的停药率影响了疗效评估，导致拉替拉韦组（范围为 32%-50%）和聚乙二醇干扰素 alfa-2a（40KD）/利巴韦林组（43%）的持续病毒学应答率相似。由于安全性原因，拉替拉韦被停用的患者比例为 28%-36%（最常见的原因是淋巴细胞减少），且严重不良事件（尤其是血液、感染、眼部事件）的患者比例与剂量相关。严重血液学不良事件（尤其是中性粒细胞减少症、淋巴细胞减少症）在拉替拉韦组更为常见。拉替拉韦/聚乙二醇干扰素 alfa-2a/利巴韦林联合组的 2 例死亡被认为可能与研究药物有关。
由于该研究显示出不可接受的获益与风险比，拉替拉韦治疗慢性丙型肝炎的进一步开发已停止（www.ClinicalTrials.gov NCT 00517439）。
