Gilead
and Achillion Announce Positive Antiviral
Activity of NS4A Antagonist in HCV,
But
Discontinue GS 9132 (ACH-806) Development FOSTER
CITY, Calif. and NEW HAVEN, Conn., Feb. 8 /PRNewswire-FirstCall/ -- Gilead Sciences
(NASDAQ: GILD) and Achillion Pharmaceuticals (NASDAQ: ACHN) today 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, PhD, 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, PhD, 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. |
