[Some of these data were reported in Jan 2011 (#msg-58589578). INX-189 is a prodrug of a monophosphate guanosine analog, similar in structure to IDX184.]
ATLANTA--(BUSINESS WIRE)-- 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.
[See actual PR for data table.]
In addition to these median reductions in viral load, clinically 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.‹
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