[INX-189 is structurally and functionally similar to IDIX’s IDX184 and VRUS’ PSI-938; all of them are prodrugs of a monophosphate nucleotide analog of guanosine. Until recently, IDIX had a clear lead in timing among these drugs, but this is no longer true insofar as IDX184 is on FDA clinical hold.
The phase-1b trial described here is unusual in that it contains two cohorts that test INX-189 in combination with ribavirin (but not IFN). Moreover, the trial includes seven days of dosing, rather than the usual three days for phase-1b studies.]
ATLANTA--(BUSINESS WIRE)-- Inhibitex, Inc. (NASDAQ: INHX), announced today that it has initiated a Phase 1b, multiple ascending dose (MAD) clinical trial of INX-189, its nucleotide polymerase inhibitor in development for the treatment of 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 anti-viral activity of INX-189 administered orally once daily for seven days in treatment naïve patients with HCV genotype 1. Each treatment cohort will include 10 patients, eight of which will receive INX-189 and two of which will receive placebo. The first cohort in the Phase 1b study will receive 9 mg of INX-189 once daily. In addition to evaluating INX-189 as monotherapy, the Company plans to evaluate two dose levels of INX-189 administered once daily for seven days in combination with ribavirin, which is one of the drugs currently approved for the treatment of HCV. The dose levels of INX-189 to be evaluated in combination with ribavirin will be determined based upon the results of the monotherapy cohorts.
“The initiation of this proof of concept study in patients with chronic hepatitis C marks an important milestone in the clinical development of INX-189,” stated Dr. Joseph Patti, Senior Vice President and Chief Scientific Officer of Inhibitex, Inc. “We believe that dosing INX-189 both as monotherapy and in combination with ribavirin in this study will enhance our ability to assess the anticipated anti-viral synergies of the two agents and allow us to better define the most appropriate doses of INX-189 to evaluate in future clinical trials.”
Inhibitex is developing a series of proprietary nucleotide inhibitors that target the RNA-dependent RNA polymerase (NS5b) of HCV. The Company believes that its nucleotides possess several pharmacological advantages over other HCV nucleosides or nucleotides in clinical development, including a more efficient conversion into their active anti-viral form, a more favorable resistance profile, and anti-viral synergy when used in combination with ribavirin. INX-189 is a protide of a 2’-C-methylguanosine analogue, which, based on in vitro data, the Company believes is the most potent HCV nucleotide polymerase inhibitor currently in clinical development. 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 anti-virals for the treatment of patients with all known genotypes of HCV.
About Inhibitex
Inhibitex, Inc. is a biopharmaceutical company focused on developing products to prevent and treat serious infectious diseases. The Company’s clinical stage pipeline includes FV-100, a bicyclic nucleoside inhibitor in Phase II development for the treatment of shingles, and INX-189, a nucleotide polymerase inhibitor in development for the treatment of chronic infections caused by hepatitis C virus (HCV). 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.‹
Inhibitex Reports Positive Interim Safety and Antiviral Data from Ongoing Phase 1b Study of HCV Nucleotide Inhibitor INX-189 -9mg and 25mg QD Doses Demonstrate Significant Reductions in HCV RNA Levels-
ATLANTA--(BUSINESS WIRE)-- Inhibitex, Inc. (Nasdaq:INHX - News) 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.
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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.
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 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 www.inhibitex.com.