In an Interim Analysis From an Ongoing Phase IIb Clinical Trial
of IDX184, an HCV Nucleotide Inhibitor, 89% of Patients Who Completed
an Additional 12 Weeks of Pegylated Interferon Plus Ribavirin Treatment
Achieved SVR4; 100% (4/4) in 100 mg Arm and 80% (4/5) in 50 mg Arm
IDX719, an HCV NS5A Inhibitor, Achieves Potent Pan-Genotypic Activity in Three-Day Proof-of-Concept Clinical Trial
CAMBRIDGE, Mass., June 19, 2012 (GLOBE NEWSWIRE) — Idenix Pharmaceuticals, Inc.
(Nasdaq:IDIX), a biopharmaceutical company engaged in the discovery and
development of drugs for the treatment of human viral diseases, today
announced results from an ongoing phase IIb study of IDX184 in
combination with pegylated interferon and ribavirin (PegIFN/RBV). Of the
first cohort of 31 patients enrolled in the study, those who achieved
an eRVR (n=18), defined as having undetectable levels of virus at 4
weeks and 12 weeks, were randomized to stop treatment after either an
additional 12 weeks (n=9) or 36 weeks (n=9) of PegIFN/RBV. Of the nine
patients who completed their 12-week PegIFN/RBV extended treatment
phase, 100% of patients (4/4) in the 100 mg arm and 80% of
patients (4/5) in the 50 mg arm achieved a sustained virologic response
four weeks after the completion of treatment (SVR4). Patients who did
not achieve an eRVR automatically entered the 36-week PegIFN/RBV
extended treatment phase which is ongoing. To date, the side effect
profile of IDX184 combined with PegIFN/RBV is consistent with that of
“We are encouraged by the initial SVR results from the phase IIb
program, which have confirmed previous data showing that IDX184 is a
potent nucleotide inhibitor with a profile supporting its potential role
as a key component of all-oral direct-acting antiviral (DAA)
combination regimens for HCV,” stated Ron Renaud,
President and Chief Executive Officer of Idenix. “We look forward to
initiating interferon-free DAA combination studies in the near term.”
IDX184 Phase IIb Study Design
In July 2011, the company initiated enrollment of
treatment-naive genotype 1 HCV-infected patients into a randomized,
double-blind, parallel group phase IIb clinical trial of IDX184. The
study features two treatment arms, either 50 mg or 100 mg of IDX184
administered once-daily for 12 weeks, each arm in combination with
PegIFN/RBV. Response-guided therapy was used to complete an additional
12 or 36 weeks of PegIFN/RBV treatment. Study objectives include safety
and tolerability, and antiviral activity endpoints.
IDX719 Proof-of-Concept Clinical Trial Data and Study Design
Idenix also announced today positive data from a three-day
proof-of-concept study evaluating IDX719, an NS5A inhibitor, in 64
treatment-naïve, genotype 1, 2, 3 or 4 HCV-infected patients. Genotype 1
patients were randomized to receive placebo, 25 mg QD (once-daily), 50
mg QD, 50 mg BID (twice-daily) or 100 mg QD for three days. Genotype 2, 3
or 4 patients were randomized to receive placebo, 50 mg BID or 100 mg
QD for three days.
IDX719 was well tolerated with no serious adverse events reported.
Treatment with IDX719 exhibited potent pan-genotypic activity across
In genotype 1 patients (n=28), mean maximal viral load reductions were 3.2 log10 IU/mL in the 25 mg QD arm, 3.7 log10 IU/mL in the 50 mg QD arm, 3.2 log10 IU/mL in the 50 mg BID arm and 3.5 log10 IU/mL in the 100 mg QD arm.
In genotype 2 patients (n=8), the mean maximal viral load reduction was 2.0 log10
IU/mL in both the 50 mg BID and 100 mg QD dose arms with a greater
variability in responses among these patients (range: 0.3 — 4.1 log10 IU/mL). The company is currently conducting pharmacokinetic and sequencing analyses to further characterize these results.
In genotype 3 patients (n=8), mean maximal viral load reductions were 3.3 log10 IU/mL in the 50 mg BID arm and 3.4 log10 IU/mL in the 100 mg QD arm.
In genotype 4 patients (n=7), mean maximal viral load reductions were 3.9 log10 IU/mL in the 50 mg BID dose arm and 3.4 log10 IU/mL in the 100 mg QD dose arm.
More detailed findings are expected to be presented at a scientific meeting in the second half of 2012.
“We are pleased to demonstrate the first clinical validation of IDX719
in patients in a multiple-dose study with robust activity across
multiple HCV genotypes,” commented Douglas Mayers,
M.D., Chief Medical Officer of Idenix. “Given these promising findings,
we look forward to initiating a phase II combination study of IDX719
with IDX184 by the end of this year.”
IDX184 is an unpartnered, novel, liver-targeted nucleotide prodrug of
2′-methyl guanosine, which includes Idenix’s proprietary liver-targeting
technology. This technology enables the delivery of nucleoside
monophosphate to the liver, leading to the formation of high levels of
nucleoside triphosphate, potentially maximizing drug efficacy and
limiting systemic side effects with low, once-daily dosing. In the
ongoing phase IIb clinical trial, IDX184 has been well tolerated with a
side effect profile similar to that of PegIFN/RBV. In the first cohort
of 31 patients, at 12 weeks in an intent-to-treat analysis, the complete
early virologic response ( < 25 IU/mL at 12 weeks) was 93% for the
100 mg IDX184 arm (n=15) and 81% for the 50 mg IDX184 arm (n=16) of the
study. The company completed enrollment of a second cohort of 36
additional patients in May 2012.
IDX719 is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro.
In 36 healthy volunteers, IDX719 was safe and well tolerated at single
doses of 5-100 mg as well as multiple doses of 100 mg for 7 days. Single
doses of IDX719 demonstrated potent pan-genotypic antiviral activity in
18 genotype 1, 2 or 3 HCV-infected patients, with greater than 3 log10 viral load reductions achieved in the 100 mg dose arm.
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