Gilead Sciences and Achillion Pharmaceuticals announced their decision to discontinue the development of GS 9132, also known as ACH-806, for the treatment of hepatitis C viral (HCV) infection, based upon preliminary data from a phase 1b/2 trial.
Preliminary data from the first cohort of the Phase 1b/2 trial indicated that the compound demonstrated antiviral activity, validating the novel anti-HCV mechanism that involves inhibition of a viral protein called NS4A, which binds to a portion of HCV protease. However, based on small elevations of serum creatinine (a marker of kidney function), which were reversible after completion of dosing, Gilead and Achillion have elected to shift their focus to the evaluation of other NS4A antagonists developed by Achillion to identify a lead candidate for development.
"GS 9132 has demonstrated antiviral activity in patients with genotype 1 HCV infection. Even at the low dose studied, we observed significant reductions in hepatitis C viral load. This validation of the mechanism of action is encouraging as we evaluate next-generation compounds for potential development," said Norbert Bischofberger, Ph.D., Executive Vice President, Research and Development, Gilead Sciences. "We look forward to our continued collaboration with Achillion."
"As part of our collaboration with Gilead, we have worked diligently to generate a number of compounds belonging to a different chemical class that demonstrate the same mechanism of action and similar in vitro potency to GS 9132. One of the most promising of these has been designated by Achillion as ACH-1095, and we are evaluating this and other compounds in preclinical studies to determine if one has the right profile to advance into clinical development," stated Milind Deshpande, Ph.D., Chief Scientific Officer of Achillion. "Our goal is to develop a novel, efficacious and safe therapeutic for HCV, and the data indicate that candidates with this mechanism may be complementary to both protease and polymerase inhibitors, as well as interferon therapies."
The GS 9132 Phase 1b/2 trial was a double-blind, randomized, placebo-controlled dose-escalation study initiated in 2006. The goal of the trial was to evaluate the antiviral activity, safety and pharmacokinetics of GS 9132 in patients with HCV genotype 1 infection. Gilead and Achillion are continuing to analyze the data from this trial. Following completion of analysis, these data will be submitted for possible presentation at an upcoming scientific conference.
In November 2004, Gilead and Achillion established an agreement granting Gilead worldwide rights for the research, development and commercialization of certain Achillion compounds for the treatment of hepatitis C. GS 9132 and ACH-1095 are small molecule inhibitors of HCV replication, which target a viral protein called NS4A. NS4A antagonism is a novel mechanism of action for HCV treatment distinct from that of protease or polymerase inhibitors currently in development. GS 9132 and ACH-1095 were discovered by Achillion, and the company completed the initial work necessary to move GS 9132 into clinical development.