is an edited excerpt from a recent Inhibitex press release describing
the study and its findings.
Reports Positive Interim Safety and Antiviral Data from Ongoing
Phase 1b Study of HCV Nucleotide Inhibitor INX-189
mg and 25 mg QD Doses Demonstrate Significant Reductions
in HCV RNA Levels
Atlanta -- January 9, 2011 -- Inhibitex, Inc. (Nasdaq: INHX)
today reported positive preliminary interim safety and antiviral
data from the first two monotherapy cohorts of its ongoing Phase
1b clinical trial of INX-189, an oral NS5b nucleotide inhibitor
being developed to treat chronic infections caused by hepatitis
C virus (HCV).
The trial, which is being conducted under an IND in the United
States, is 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, for the treatment of HCV genotype 1 treatment
naive patients. Each treatment cohort in the study is comprised
of 10 patients, eight that receive INX-189 and two that receive
placebo. In addition to the 9 mg and 25 mg dose cohorts, the
company plans to enroll up to three more INX-189 monotherapy
cohorts in the study, as well as two cohorts that will receive
different doses of INX-189 once daily for seven days in combination
INX-189, dosed once-daily at 9 mg and 25 mg for seven days,
demonstrated potent antiviral activity with a mean HCV RNA reduction
from baseline levels of -0.71 and -1.03 log10 IU/mL, respectively.
The mean HCV RNA decline from baseline levels observed in patients
that received placebo was -0.06 log10 IU/mL. The HCV RNA declines
from baseline were statistically significant from placebo, with
p-values of 0.0156 and 0.0006 in the 9 mg and 25 mg cohorts,
respectively. In addition to the mean reductions in viral load,
clinically meaningful decreases in alanine transaminase (ALT)
levels were observed for patients receiving INX-189 at both
dose levels and no patients experienced viral breakthrough.
HCV log10 IU/mL RNA
Viral Load Decline after 3 doses
HCV log10 IU/mL RNA
Viral Load Decline after 7 doses
of Patients with > 1 log decline
in HCV log10 IU/mL RNA
QD = once daily
Preliminary assessments of the data available from the first
two cohorts in the Phase 1b study indicate that INX-189 was
well tolerated. There were no serious adverse events reported,
no discontinuations due to an adverse event, and no adverse
events related to changes in clinical laboratory evaluations.
All reported adverse events were mild or moderate and were not
dose dependent. In addition, the pharmacokinetics of the 9 mg
and 25 mg doses in HCV-infected patients were comparable to
those observed in healthy volunteers, and continue to support
the evaluation of INX-189 as a once-daily therapy.
"We are pleased with the interim results of the trial to-date
and the rapid and potent antiviral activity demonstrated at
these low doses of INX-189," commented Joseph M. Patti,
PhD, Inhibitex's CSO and Senior Vice-President of Research.
"We look forward to completing the remaining monotherapy
cohorts and evaluating the potential antiviral synergies of
INX-189 in combination with ribavirin in this ongoing study,
and anticipate reporting additional safety, antiviral and pharmacokinetic
data from the study upon its completion later this quarter."
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
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-methylguanosine analogue. The
company believes that preclinical and clinical studies of INX-189
completed to-date support its potential as a potent, once-daily
oral therapy amenable to combination with other antivirals for
the treatment of patients with all known genotypes of HCV.
In a Phase 1a study, 42 healthy volunteers received either a
single oral dose of INX-189, ranging from 3 mg to 100 mg, or
placebo. The company plans to present detailed results from
this trial during a future scientific meeting. Preliminary data
from the trial demonstrated the following:
INX-189 was well tolerated at all dose levels;
drug-related serious adverse events;
dose-related trends in frequency or type of adverse events;
adverse events occurring in more than one subject were
headache, nasal congestion, ecchymosis [bruising], and
grade II or higher laboratory abnormality adverse events;
data supported INX-189's potential for once-daily dosing.
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 II 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
Inc. Inhibitex Reports Positive Interim Safety and Antiviral Data
from Ongoing Phase 1b Study of HCV Nucleotide Inhibitor INX-189.
Press release. January 9, 2011.