The Era of Direct-acting Antivirals Has Begun

The Beginning of the End for HCV?

Marie-Louise Vachon, M.D., M.Sc.; Douglas T. Dieterich, M.D.


Semin Liver Dis. 2011;31(4):399-409. 

In This Article

ACH-0141625 (ACH-1625)

ACH-1625 is an inhibitor of the HCV NS3 protease. ACH-1625 exhibits rapid and selective distribution to the liver and has high liver/plasma ratios. In phase Ib, 5 days of ACH-1625 monotherapy at doses ranging from 200 to 600 mg twice daily or 400 to 600 mg once daily led to mean maximal reductions in HCV RNA ranging from 3.1 log10 to 4.25 log10.[21]

This PI is currently in phase IIa of clinical development to evaluate its safety, tolerability, and antiviral activity in combination with pegIFN and RBV in patients with HCV genotype 1 naïve to treatment. This study has two segments. Segment 1 compares three different dosages of ACH-1625, 200 mg, 400 mg, and 800 mg once daily with placebo in combination with pegIFN/RBV for 28 days followed by pegIFN/RBV for a total duration of 48 weeks in 64 patients with HCV genotype 1. Segment 2 compares the same three dosing regimens to placebo for 12 weeks followed by 36 weeks of pegIFN/RBV. Week 4 results of Segment 1 showed achievement of rapid virologic response (RVR) in 74 to 81% of patients compared with 20% of patients receiving placebo/pegIFN/RBV. Reductions in HCV RNA on ACH-1625 ranged from 4.63 log10 to 4.96 log10 IU/mL after 4 weeks of triple therapy compared with 2.25 log10 IU/mL with placebo/pegIFN/RBV. It is worth noting that the majority of the patients enrolled were carriers of the unfavorable IL28B CT or TT genotypes and infected with HCV genotype 1a. The safety profile was comparable between all groups. No viral breakthroughs were observed during the first 4 weeks.


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