HCV NS3/4A Protease Inhibitor

Program Overview

As part of its proprietary hepatitis C (HCV) inhibitor program, Achillion discovered and optimized the investigational compound, ACH-2684. ACH-2684 is a highly potent, second-generation NS3/4A protease inhibitor. Achillion retains worldwide commercial rights to ACH-2684. The compound has been advanced as a development candidate for the treatment of chronic HCV and has completed Phase 1 development. Achillion recently announced plans to initiate a Phase 2, all-oral, interferon-free combination study with ACH-2684 and the second-generation NS5A inhibitor, ACH-3102, in GT 1b HCV patients over a treatment duration of 8 weeks in mid-2014 to enable future combination studies.


ACH-2684 in vitro retains potency against all HCV genotypes (GT) and exhibits equipotent activity against HCV GT 1a and 1b at an IC50 of approximately 100 picomolar.


ACH-2684 is metabolically stable and is rapidly and extensively partitioned in the liver, supporting once-daily dosing without the need for boosting.


ACH-2684 was shown to be safe and well-tolerated in both healthy volunteers and HCV-infected patients during Phase 1 studies.

The safety profile of ACH-2684 to date supports further clinical development.


In Phase 1b studies, once-daily doses of ACH-2684 for 3 days displayed robust antiviral activity in cirrhotic and non-cirrhotic subjects with respective 3.67 log10 and 3.73 log10 mean maximal reductions in HCV RNA.


ACH-2684 has demonstrated a high barrier to resistance in vitro, retaining potent activity against commonly observed, highly-resistant, protease inhibitor-induced mutations at positions 155, 156, and 168.


In vitro testing has shown ACH-2684 is synergistic when combined with other inhibitors of HCV including NS5A inhibitors and NS5B nucleoside polymerase inhibitors.

For more information about the highly potent, second-generation NS3/4A protease inhibitor, ACH-2684, please see the Related Links on this page or visit Resources.

ACH-2684 is an investigational compound. Its safety and efficacy have not been established. (Updated January 2014)

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