HCV NS5A Inhibitor
In 2011, Achillion discovered and nominated the investigational compound, ACH-3102. ACH-3102 is a structurally distinct second-generation NS5A inhibitor which has been granted Fast Track designation from the U.S. Food and Drug Administration (FDA) for the treatment of chronic hepatitis C (HCV). An ongoing Phase 2 clinical trial is evaluating the all-oral, interferon-free combination of ACH-3102 and Achillion's next-generation NS3/4A protease inhibitor, sovaprevir, with ribavirin (RBV), for 12 weeks, in genotype 1 (GT 1) HCV patients. Achillion recently announced plans to initiate a Phase 2, all-oral, interferon-free combination study with ACH-3102 and the potent second-generation NS3/4A protease inhibitor, ACH-2684, in GT1b HCV-infected patients over a treatment duration of 8 weeks in mid-2014. Further, Achillion announced plans to initiate a pilot Phase 2 study evaluating the combination of ACH-3102 and sofosbuvir in treatment-naïve HCV patients over treatment durations of 8 weeks or less, with an objective of optimizing the use of ACH-3102 in nucleotide-based regimens, and expediting the development of the combination of ACH-3102 with Achillion’s proprietary nucleotide NS5B polymerase inhibitor, ACH-3422. Achillion retains worldwide commercial rights to ACH-3102.
ACH-3102 has picomolar potency and has displayed pan-genotypic activity against all subtypes of HCV in vitro.
ACH-3102 has demonstrated robust antiviral activity with a greater than 3.7 log10 mean maximal reduction of HCV RNA with a single dose in genotype (GT) 1a patients, the harder to treat GT1 subtype.
ACH-3102 has an extended half-life that supports once-daily dosing.
ACH-3102 was shown to be well tolerated with no serious adverse events reported through 12 weeks of treatment in Phase 2 studies to date.
The safety profile of ACH-3102 to date supports further clinical development.
ACH-3102 is the only NS5A inhibitor to achieve a sustained virologic response (SVR) in GT 1b HCV-infected patients without the co-administration of interferon or a second direct-acting antiviral (DAA) agent.
100% of treatment-naive GT1b patients achieved SVR12 in the Phase 2 -007 Study, evaluating the interferon-free combination of ACH-3102 and the next-generation NS3/4A protease inhibitor sovaprevir with ribavirin (RBV) for 12 weeks.
ACH-3102 provides a high pharmacologic barrier to resistance with enhanced activity against the most common resistant variants to emerge during NS5A treatment, including those occurring at positions 31 and 93.
In clinical studies to date, there have been no on-treatment viral breakthroughs in GT1b HCV patients evaluated.
In vitro testing has shown ACH-3102 is synergistic when combined with other inhibitors of HCV, including NS5B polymerase inhibitors and NS3/4A protease inhibitors.
For more information about the second-generation NS5A inhibitor, ACH-3102, please see the Related Links on this page or visit Resources.
ACH-3102 is an investigational compound. Its safety and efficacy have not been established. (Updated March 2014)