Valopicitabine Shows Potential Therapeutic Response in the Treatment of Genotype 1 Hepatitis C Patients
By Idenix Pharmaceuticals
Apr 14, 2005, 20:33

Idenix Pharmaceuticals, Inc. (Nasdaq: IDIX - News), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral and other infectious diseases, today announced preliminary phase IIa clinical trial data for valopicitabine (NM283) in treatment naive genotype 1 hepatitis C patients.

In this phase IIa clinical trial, 9 patients receiving the combination of valopicitabine and pegylated interferon have reached 24 weeks of treatment, and achieved a mean reduction in serum HCV RNA of 4.5 log10, or more than 99.99 percent. These data will be presented at the 40th Annual Meeting of the European Association for the Study of the Liver (EASL) in Paris, France on Sunday, April 17 at 12:00 p.m. Central European Time (CET) by Nezam Afdhal, M.D., of Harvard Medical School.

In January, Idenix reported 12-week data on 12 patients receiving valopicitabine plus pegylated interferon combination therapy. Of the 12 patients previously reported, nine patients have now reached 24 weeks of combination treatment and have experienced substantial additional antiviral response. In eight out of the nine patients, levels of virus have decreased to below 600 IU/mL, which is the lower quantification limit of the Amplicor(TM) PCR assay, an assay typically used by physicians to monitor the effectiveness of hepatitis C treatment. Six of the nine patients achieved undetectable levels of virus utilizing the real-time TaqManŽ PCR assay, an assay with a high level of sensitivity, which has a detection limit of 10 IU/mL.

"This is the first time that we are seeing 24-week data for an antiviral drug directly targeting a specific enzyme of the hepatitis C virus," said Nezam Afdhal, M.D., a principal investigator in the phase IIa valopicitabine trials and Chief of Hepatology at Beth Israel Deaconess Medical Center in Boston and Associate Professor at Harvard Medical School. "These preliminary data are promising and suggest that direct antiviral drugs, such as valopicitabine, could set a new treatment standard in hepatitis C, by offering hepatitis C patients, particularly patients infected with HCV genotype 1, potentially improved clinical benefit with fewer side effects."

Clinical Trial Design: A total of 30 patients in the phase IIa clinical trial were enrolled and randomized to one of two treatment arms so that 18 patients receive the combination of valopicitabine and pegylated interferon and 12 patients receive valopicitabine monotherapy. Patients on combination treatment receive a titrating dose of valopicitabine once a day up to 800 mg by day 8 and then continue this dose throughout the treatment period. Additionally, a Peg-IntronŽ dose of 1.0 mcg/kg is administered once a week starting on day 8. Enrolled patients are treatment naive, HCV genotype 1, with baseline viral load greater than 5 log10 IU/mL and alanine aminotransferase (ALT) levels less than 5 times the upper limit of normal. With the agreement of the clinical trial investigators and submission of protocol amendments to the United States Food and Drug Administration (FDA), Idenix has extended the treatment duration of this clinical trial from the initially planned 28 days, to 12 weeks, then 24 weeks and finally to 48 weeks based on the interim results.

Clinical Trial Results: Of the 30 patients enrolled, one has recently begun treatment, 25 have reached 12 weeks of treatment and four patients discontinued treatment prior to week 12. Two of these withdrawals were interferon-related, one patient consented only to participate in the initial 28-day clinical trial and one was lost to follow-up. Results for the group that have reached 12 weeks of treatment are consistent with the previously announced 12-week findings reported in a company press release on January 10, 2005. The updated 12-week data demonstrate a mean HCV RNA reduction from baseline of 3.01 log10 IU/mL, or 99.9 percent, for the 16 patients in the combination treatment group, and 0.87 log10 IU/mL, or 86.5 percent, for the 12 patients in the valopicitabine monotherapy group.

To date, 10 patients have reached 24 weeks of treatment. Nine patients in the valopicitabine plus pegylated interferon treatment group have completed 24 weeks of treatment. The mean HCV RNA reduction from baseline for those patients was 4.5 log10 IU/mL, or more than 99.99 percent. One patient in the monotherapy group continued treatment after week 12, and after 24 weeks of treatment experienced an HCV RNA reduction from baseline of 1.9 log10 IU/mL. Six of the nine patients receiving the combination treatment achieved virus levels below the level of detection by real-time PCR, an assay with a high level of sensitivity (<10 iu ml/

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