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 naïve 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 with ribavirin.
INX-189, dosed once-daily at 9mg and 25mg 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.
|Cohort||Mean HCV log10 IU/mL RNA
Viral Load Decline after 3 doses
|Mean HCV log10 IU/mL RNA
Viral Load Decline after 7 doses
|# of Patients with >1 log decline
in HCV log10 IU/mL RNA
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 9mg and 25mg 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, Ph.D., 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 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-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;
- No drug-related serious adverse events;
- No dose-related trends in frequency or type of adverse events; adverse events occurring in more than one subject were headache, nasal congestion, ecchymosis, and presyncope;
- No grade II or higher laboratory abnormality adverse events; and
- Pharmacokinetic data supported INX-189’s potential for once-daily dosing.