Toniutto Pierluigi, Fabris Carlo, Bitetto Davide, Fumolo Elisa, Fornasiere Ezio, Pirisi Mario
University of Udine, Internal Medicine, DPMSC, Medical Liver Transplant Unit, Piazzale Santa Maria della Misericordia 1, 33100 Udine, Italy.
IDrugs. 2008 Oct;11(10):738-49.
Roche Holding AG is developing R-1626, an oral nucleoside inhibitor of HCV RNA polymerase. R-1626 has been demonstrated to be well absorbed and rapidly converted to the active component R-1479. The compound has demonstrated a strong capacity to inhibit HCV replication in vitro and in vivo, without the rapid development of viral resistance. After 4 weeks of treatment with R-1626 in combination with PEG-IFN plus ribavirin in treatment-naïve patients with genotype 1 HCV infection, HCV RNA could no longer be detected in approximately 74% of patients, compared with 5% of patients treated with PEG-IFN plus ribavirin alone, indicating the high potency of R-1626 to induce HCV RNA viral load reductions. R-1626 was generally well tolerated, although severe side effects of neutropenia were observed at high doses. A phase IIb clinical trial was ongoing at the time of publication to test the efficacy of R-1626 in combination with a standard or lower dose of PEG-IFN and ribavirin in HCV genotype 1-infected patients. Given its potent antiviral effect with an apparent high genetic barrier, R-1626 represents an important advancement in improving the outcome of patients with chronic HCV infection.
罗氏控股公司正在研发R - 1626，一种丙型肝炎病毒（HCV）RNA聚合酶的口服核苷抑制剂。R - 1626已被证明吸收良好，并能迅速转化为活性成分R - 1479。该化合物在体外和体内均显示出强大的抑制HCV复制的能力，且不会迅速产生病毒耐药性。在初治的1型HCV感染患者中，将R - 1626与聚乙二醇干扰素（PEG - IFN）加利巴韦林联合治疗4周后，约74%的患者中已无法检测到HCV RNA，而单独使用PEG - IFN加利巴韦林治疗的患者中这一比例为5%，这表明R - 1626具有很高的降低HCV RNA病毒载量的效力。R - 1626总体耐受性良好，尽管在高剂量时观察到了严重的中性粒细胞减少副作用。在发表时，一项IIb期临床试验正在进行，以测试R - 1626与标准剂量或较低剂量的PEG - IFN和利巴韦林联合用于HCV 1型感染患者的疗效。鉴于其强大的抗病毒作用以及明显的高遗传屏障，R - 1626代表了改善慢性HCV感染患者治疗结果方面的一项重要进展。
