Positive top-line data from Inhibitex INX-189 Phase 1b trial against HCV

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.

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."