Idenix Pharmaceuticals, Inc., a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, announced interim data from a 14-day, phase 2a clinical trial evaluating IDX184, a novel liver-targeted nucleotide prodrug of 2’-methyl guanosine monophosphate, in HCV-infected patients. Data are being presented at the 45th annual meeting of the European Association for the Study of the Liver being held in Vienna, Austria.
The phase IIa clinical trial, initiated in the fourth quarter of 2009, is a randomized, double-blind, placebo-controlled, sequential dose-escalation study evaluating the safety, tolerability, pharmacokinetics and antiviral activity of IDX184 in combination with PegIFN/RBV in treatment-naïve HCV genotype 1-infected patients. Patients receive a daily dose of IDX184 or placebo, plus pegIFN/RBV for 14 days and then continue on PegIFN/RBV for an additional 14 days. The study is evaluating four dosing regimens of IDX184 ranging from 50 to 200 mg per day. In the 100 mg and 200 mg cohorts, once daily (QD) and twice daily (BID) regimens are compared. Each cohort includes 20 patients randomized 4:1, IDX184:placebo.
In the data presented today, IDX184 demonstrated potent dose-dependent antiviral activity when combined with PegIFN/RBV. At Day 14, mean (± standard deviation) viral load reductions were 1.2 (± 1.1), 2.7 (± 1.3), 4.0 (± 1.7) and 4.2 (± 1.9) log10 IU/mL in the placebo (n=8), 50 mg IDX184 QD (n=16), 50 mg IDX184 BID (n=8) and 100 mg IDX184 QD (n=8) cohorts, respectively. Half of the subjects receiving a total daily dose of 100 mg IDX184 achieved undetectable virus levels (< 15 IU/mL) by Day 14. Liver injury parameters (ALT and AST) improved (normalized) with all doses of IDX184. Antiviral activity and safety parameters measured after a total daily dose of 100 mg IDX184 did not differ between a QD or BID dosing regimen. The side effect profile of the three-drug combination was consistent with the known side effect profile of PegIFN/RBV alone. The most common adverse events reported were fatigue, myalgia, headache and nausea. No virologic breakthrough was observed during treatment with IDX184 in combination with PegIFN/RBV.
“We are very encouraged by these interim data for IDX184 combined with pegylated interferon and ribavirin as the viral load reductions for the 100 mg cohorts are on par with the first-generation nucleoside in development but at a fraction of the dose,” said Douglas Mayers, M.D., Idenix’s executive vice president and chief medical officer. “We are currently enrolling the 150 mg once-daily dose cohort and look forward to reporting full data later this year. We believe that with the favorable antiviral activity, safety and resistance profile seen to date, IDX184 could be a potential component of future direct-acting antiviral combination regimens.”
“With a high barrier to resistance and broad genotypic coverage, nucleosides and/or nucleotides could become an important part of future combination therapy for hepatitis C patients,” said Dr. Fred Poordad, a principal investigator in the study, Chief of Hepatology at the Liver Disease and Transplant Center at Cedars-Sinai Medical Center in Los Angeles. “The interim 50 and 100 mg cohort data for IDX184 in combination with pegylated interferon and ribavirin have been promising and we look forward to the continued clinical development of this drug candidate.”
Date: April 15, 2010
Source: Idenix Pharmaceuticals, Inc.