Genotype 1 HCV-infected patients were randomized to 3 days of once-daily (QD) dosing with placebo (n = 12) or GS-5885 1 mg (n = 10), 3 mg (n = 10), 10 mg (n = 20), 30 mg (n = 10), or 90 mg (n = 10). Plasma samples for pharmacokinetics, HCV RNA, and NS5A sequencing were collected through day 14.
GS-5885 was well tolerated and resulted in median maximal reductions in HCV RNA ranging from 2.3 log<sub>10sub> IU/ml (1 mg QD) to 3.3 log<sub>10sub> IU/ml (10 mg QD in genotype 1b and 30 mg QD). E<sub>maxsub> modeling indicated GS-5885 30 mg was associated with >95%of maximal antiviral response to HCV genotype 1a. HCV RNA reductions were generally more sustained among patients with genotype 1b
During 3 days of monotherapy, low doses of GS-5885 demonstrated significant antiviral activity in genotype 1a and 1b HCV-infected patients. GS-5885 is currently being evaluated in combination with direct antiviral regimens with and without peginterferon.