Rapid Decline of HCV RNA in Patients Treated with VX-950
VX-950 (now named telaprevir) is an oral antiviral agent that specifically inhibits the NS3/4A protease of hepatitis C virus (HCV). Data presented at several recent conferences show that VX-950 has antiviral activity in vitro and in humans.
Results from a Phase I, placebo-controlled, double-blind clinical trial of VX-950 were published in the October 2006 issue of Gastroenterology. The study evaluated the antiviral activity, pharmacokinetics, and safety of VX-950 in 34 patients with chronic genotype 1 HCV; 27 (79%) had failed prior hepatitis C treatment. Participants were randomly assigned to receive placebo or VX-950 at one of the following doses for 14 days:
450 mg every 8 hours
750 mg every 8 hours
1250 mg every 12 hours.
VX-950 was well tolerated and had substantial antiviral effects.
HCV viral load dropped by at least 2 logs in all 28 patients treated with VX-950 and by at least 3 logs in 26 of these patients (93%).
In the 750 mg dose group, which had the highest trough plasma drug concentrations, the median reduction of HCV RNA was 4.4 logs after 14 days.
In the 450 mg and 1250 mg groups, the maximal effect was seen between days 3 and 7 of dosing, and median HCV RNA increased between days 7 and 14.
At day 14, the median reduction was 2.4 logs in the 450 mg group and 2.2 logs in the 1250 mg group.
Median alanine aminotransferase (ALT) levels decreased during therapy in all VX-950 arms.
HCV variants resistant to VX-950 were observed in some patients.
In conclusion, the authors wrote, "VX-950 was well tolerated and demonstrated substantial antiviral activity. Some patients had viral breakthrough during dosing, related to selection of variants with decreased sensitivity to VX-950. The results support further studies of VX-950 in patients with chronic hepatitis C."
H W Reesink, S Zeuzem, C J Weegink, and others. Rapid Decline of Viral RNA in Hepatitis C Patients Treated With VX-950: A Phase Ib, Placebo-Controlled, Randomized Study. Gastroenterology 131(4): 997-1002. October 2006.