一個新穎、高效的C肝病毒蛋白酶抑制劑：TG-2349（伏拉瑞韋）

A Novel and High Potent HCV Protease Inhibitor: TG-2349 (Furaprevir)

TG-2349（通用名：伏拉瑞韋）是一個醯基磺醯胺類的新型C肝病毒蛋白酶抑制劑，對6種不同基因型的蛋白酶均有良好的抑制活性，也能有效壓制常見的抗藥性突變株。已完成的臨床I期及臨床II期試驗顯示，TG-2349有良好的安全性與耐受性；每日服用一劑，血中藥物濃度遠高過抑制病毒的程度；連續服用3天後，基因型第1a、2、4、或6型患者體內病毒下降量達2.8-3.6 log。對第1b亞型（佔亞洲病人60%以上）下降量更高達4.4 log。當與C肝標準療法（長效型干擾素+雷巴威林）合併時，對基因型1b患者的治療時間可以縮短到12週，療效提升至90%（SVR12）以上，證實了TG-2349是一個新穎且具高療效的C肝病毒抑制劑。臨床開發包含TG-2349與其他DAA共用的全口服療法也正在積極進行中。

TG-2349 (INN name Furaprevir) is a novel sulfonamide class of HCV NS3/4A protease inhibitor. It is potent against both wild type and mutant proteases across genotype 1 to 6 in vitro. TG-2349 is generally safe and well tolerated in phase I/II clinical studies to date. PK results supported QD dosing. In a proof-of-concept trial against treatment-naive patients with different HCV genotypes, 3-day dosing of TG-2349 demonstrated HCV viral load reductions of 2.8 - 3.6 log in genotypes 1a/2/4/6 subjects. Reductions of 4.4 log were achieved in GT-1b subjects, which consists of ＞60% of Asian HCV patients. Total treatment durations can be reduced from over 24 weeks to 12 weeks when combining TG-2349 with the current SOC peginterferon/ribavirin. SVR24 of ＞90% was observed in Taiwanese naive GT-1b subjects. Development of TG-2349-containing all-oral, IFN-free HCV treatments are underway.