Rapid and sharp decline in HCV upon monotherapy with NS3 protease inhibitor, ACH-1625

被引:13
作者
Agarwal, Atul [1 ]
Zhang, Bao [1 ]
Olek, Elizabeth [1 ]
Robison, Heather [1 ]
Robarge, Lisa [1 ]
Deshpande, Milind [1 ]
机构
[1] Achillion Pharmaceut Inc, New Haven, CT USA
关键词
EFFICACY;
D O I
10.3851/IMP2359
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Background: ACH-1625 is a linear peptidomimetic inhibitor that non-covalently binds to HCV NS3 protease with high potency and specificity. Short-term monotherapy of HCV genotype-1 infection with ACH-1625 was found to be safe and resulted in >= 3.3 log(10) IU/ml mean viral load reduction. These viral load decay data were analysed to compare HCV dynamics with prior reports and estimate the antiviral efficiency of ACH-1625. Methods: Drug efficiency was estimated by analysing the viral decay following initiation of up to 5 days of monotherapy with ACH-1625 in 36 chronically infected HCV genotype-1 patients. During this monotherapy study, ACH-1625 was administered either twice-a-day for 4.5 days or once daily for 5 days at 5 different dose levels in 36 patients. Results: A sharp viral decay during the first 48 h following the initiation of ACH-1625 treatment afforded high drug efficiency estimates (>= 0.9934). In addition, an increase in the estimated drug efficiency was observed with increasing ACH-1625 dose. The observed anti-HCV response was fairly uniform in this proof-of-concept study across the population of 36 patients. Conclusions: Estimates of the treatment-independent viral kinetics parameters were consistent with prior reports and the estimated drug efficiency of ACH-1625 monotherapy was very high (>= 0.9934) in fasted and fed states.
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收藏
页码:1533 / 1539
页数:7
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