of HCV Nucleotide Inhibitor INX-189
Potent Dose-Dependent Antiviral Activity Demonstrated with Once-Daily
Administration-
-Viral Load Declines in Combination with Ribavirin Confirm Antiviral Synergy-
ATLANTA--(BUSINESS WIRE)--Mar 31, 2011 - Inhibitex, Inc.
(Nasdaq: INHX) today reported positive top-line safety and
antiviral data from its multiple ascending dose Phase 1b clinical
trial of INX-189, an oral nucleotide polymerase inhibitor being
developed to treat chronic infections caused by hepatitis C virus
(HCV).
The trial was a double-blind, placebo-controlled, dose
escalation study designed to evaluate the safety, tolerability,
pharmacokinetics and antiviral activity of INX-189, administered
orally once-daily for seven days, in HCV genotype 1 treatment
naïve patients. A total of 70 subjects were randomized into
the trial among seven different dosing cohorts, including five
monotherapy treatment arms and two arms of adjunctive treatment
with ribavirin (RBV). Each treatment cohort in the study was
comprised of 10 patients, eight of whom received INX-189 and two
that received placebo.
INX-189, dosed once-daily at 9, 25, 50 and 100 mg for seven
days, demonstrated potent and dose-dependent antiviral activity
with median HCV RNA reductions from baseline of -0.64, -1.00,
-1.47, and -2.53 log10 IU/mL, respectively. INX-189,
dosed once-daily at 50 mg for one day, followed by 9 mg for six
days, achieved a median HCV RNA reduction from baseline of -0.50
log10 IU/mL. The median HCV RNA decline from baseline
observed in patients that received placebo was -0.20
log10 IU/mL. INX-189, dosed once-daily in combination
with RBV for seven days at 9 mg and 25 mg, resulted in median HCV
RNA reductions from baseline of -0.75 and -1.56 log10
IU/mL, respectively. The median HCV RNA decline from baseline
observed in patients that received placebo and RBV was 0.04
log10 IU/mL.
Cohort (INX-189 QD) | Median HCV log10 IU/mL RNA Viral Load Decline after 3 doses | Median HCV log10 IU/mL RNA Viral Load Decline after 7 doses | Range Day 7 HCV log10 IU/mL RNA | ||||||||||||
Placebo (n=10) | 0.25 | -0.20 | 0.60 to -0.30 | ||||||||||||
9 mg (n=7) | -0.29 | -0.64 | -0.19 to -1.06 | ||||||||||||
25 mg (n=8) | -0.85 | -1.00 | -0.56 to -1.58 | ||||||||||||
50 mg (n=8) | -1.34 | -1.47 | -1.17 to -2.30 | ||||||||||||
100 mg (n=8) | -1.46 | -2.53 | -1.35 to -2.78 | ||||||||||||
50 mg x 1 day 9 mg x 6 days (n=7) | -0.46 | -0.50 | 0.11 to -0.88 | ||||||||||||
RBV with Placebo (n=4) | -0.13 | 0.04 | 1.47 to -0.61 | ||||||||||||
9 mg with RBV (n=7) | -0.45 | -0.75 | -0.35 to -0.93 | ||||||||||||
25 mg with RBV (n=8) | -1.35 | -1.56 | -0.77 to -2.68 | ||||||||||||
meaningful decreases in alanine transaminase (ALT) levels were
observed for patients receiving INX-189 at all dose levels, and no
patients experienced viral breakthrough.
Additional data available from the Phase 1b study indicate that
INX-189 was generally well tolerated. There was one serious adverse
event reported in a subject treated with RBV and placebo (atrial
fibrillation in a subject with a previous history). All other
reported adverse events were mild or moderate, with the most common
adverse event in INX-189 treated subjects being headache. There
were no discontinuations of treatment due to adverse events and
there were no adverse events related to changes in clinical
laboratory evaluations or ECGs.
“Nucleotide polymerase inhibitors are likely to be a key
component of combination direct antiviral therapy,” stated
Dr. Eric Lawitz, President and Medical Director at Alamo Medical
Research, San Antonio, Texas and a principal investigator of the
Phase 1b study. “Further, the antiviral activity observed at
the low INX-189 doses evaluated is promising, provides proof of
concept, and provides the foundation for future studies.”
“The potent antiviral activity in monotherapy and the
synergistic activity observed in combination with RBV support our
belief that INX-189 has the potential to play a pivotal role in
future HCV combination therapy,” commented Joseph M. Patti,
Ph.D., Inhibitex's CSO and Senior Vice-President of Research.
“We believe these data, taken together with the successful
completion of our 13-week GLP toxicology studies, support advancing
INX-189 into Phase 2 clinical trials later this year.”
About HCV and INX-189
Hepatitis C is a disease of the liver caused by HCV. It is
estimated that over 4 million Americans and 170 million individuals
worldwide are infected with HCV, the majority of which represent
chronic infections that can cause liver disease, cirrhosis and
cancer, and is the leading cause of liver transplants in the United
States.
Inhibitex is developing a series of proprietary nucleotide
inhibitors that target the RNA-dependent RNA polymerase (NS5b) of
HCV. INX-189 is a protide of a 2'-C-methyl guanosine
analogue. The Company believes that preclinical and clinical
studies of INX-189 completed to-date support its potential as a
potent, once-daily, low dose oral therapy amenable to combination
with other antivirals for the treatment of patients with all known
genotypes of HCV.
About Inhibitex
Inhibitex, Inc. is a clinical stage biopharmaceutical company
focused on developing products to prevent and treat serious
infectious diseases. In addition to INX-189, the Company's clinical
stage pipeline includes FV-100, a bicyclic nucleoside inhibitor in
Phase 2 development for the treatment of shingles. The Company also
has additional HCV nucleotide polymerase inhibitors in various
stages of preclinical development, and has licensed the use of its
proprietary MSCRAMM® protein platform to Pfizer for
the development of active staphylococcal vaccines. For additional
information about the Company, please visit
www.inhibitex.com.
Safe Harbor Statement
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of 1995
that involve substantial risks and uncertainties. All statements,
other than historical facts included in this press release,
including statements regarding: the likelihood of nucleotide
polymerase inhibitors being a key component of combination direct
antiviral therapy; the Company's belief that INX-189 has the
potential to play a pivotal role in future HCV combination therapy;
the Company's belief that the Phase 1b data, taken together with
the successful completion of its 13-week GLP toxicology studies,
support advancing INX-189 into Phase 2 clinical trials later this
year; and the potential of INX-189 as a potent, once-daily low dose
oral therapy amenable to combination with other antivirals for the
treatment of patients with all known genotypes of HCV, are forward
looking statements. These intentions, expectations, or results may
not be achieved in the future and various important factors could
cause actual results or events to differ materially from the
forward-looking statements that the Company makes, including the
risk of ongoing or future clinical studies of other nucleotide
polymerase inhibitors in development not supporting their future
development; the risk of future preclinical or clinical studies of
INX-189 not supporting its further development for lack of safety,
tolerability, antiviral activity, or any other reason; INX-189 not
demonstrating sufficient anti-viral activity against HCV in future
clinical trials with a once-daily dose in combination with other
antiviral drugs; either the Company, the FDA, a safety review board
or an investigational review board suspending or terminating the
clinical development of INX-189 at any time for lack of safety,
tolerability, anti-viral activity, or any other reason; obtaining,
maintaining and protecting the intellectual property incorporated
into and supporting the commercial viability of the Company's
product candidates; and other cautionary statements contained
elsewhere herein and in its Annual Report on Form 10-K for the year
ended December 31, 2010, as filed with the Securities and Exchange
Commission, or SEC, on March 16, 2011. Given these uncertainties,
you should not place undue reliance on these forward-looking
statements, which apply only as of the date of this press
release.
There may be events in the future that the Company is unable to
predict accurately, or over which it has no control. The Company's
business, financial condition, results of operations and prospects
may change. The Company may not update these forward-looking
statements, even though its situation may change in the future,
unless it has obligations under the Federal securities laws to
update and disclose material developments related to previously
disclosed information. The Company qualifies all of the information
contained in this press release, and particularly its
forward-looking statements, by these cautionary statements.
Inhibitex® and MSCRAMM® are
registered trademarks of Inhibitex, Inc.
Contact: Inhibitex, Inc.
Russell H. Plumb, 678-746-1136
Chief Executive Officer
rplumb@inhibitex.com
or
The Trout Group
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