Idenix Announces Promising Data for Hepatitis C Drugs IDX184 and IDX719

Interim findings from a Phase 2b study show that 8 out of 9 genotype 1 chronic hepatitis C patients treated with Idenix Pharmaceuticals' experimental HCV polymerase inhibitor IDX184 with continued pegylated interferon/ribavirin through week 24 had undetectable viral load 4 weeks after competing therapy. Another trial found that the NS5A inhibitor IDX719 has activity against all HCV genotypes.

The advent of direct-acting antivirals has ushered in a new era of hepatitis C treatment. While the first direct-acting drugs are being used in combination with pegylated interferon/ribavirin, development of agents that target different steps of the HCV lifecycle offers the prospect of all-oral regimens without interferon. With this in mind, several companies are working on a portfolio of experimental agents with diverse targets.

Below is an edited excerpt from a recent Idenix press release describing 2 such studies and their findings.

Idenix Announces Positive Clinical Data for HCV Drug Candidates IDX184 and IDX719

• 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 -- 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 PegIFN/RBV alone.

"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 genotypes:

• n 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, MD, 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."

About IDX184

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.

About IDX719

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.

About Idenix

Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical Company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of patients with HCV. For further information about Idenix, please refer to www.idenix.com.

6/29/12

Source

Idenix Pharmaceuticals. Idenix Announces Positive Clinical Data for HCV Drug Candidates IDX184 and IDX719. Press release. June 19, 2012.