The company, Idenix, distributed the Press Announcement below today.
I am at EASL in Paris and these study results for NM283 are perhaps the most exciting so far that I’ve seen here in what otherwise is not a very exciting conference. For partial responders to peginterferon, the combination of PEG plus NM283 may be just what’s needed to get some patients to SVR.
As expected hepatitis B is getting much attention because treatment for HBV is high profile due to 4 FDA approved drugs, most recently entecavir and a bunch of drugs in earlier stages of development. Crucial issues that will need to be addressed for HVC are drug resistance, when to begin, strategizing treatment sequencing, combination therapy will likely emerge as important, when or if to use peginterferon as firstline therapy. In HBV/HIV coinfection, when to begin HBV therapy is more controversial since 3Tc and Truvada (tenofovir/FTC) are effective against HIV & HBV, but when do you start HBV therapy is a question? Jules Levin.
PS My big purchase here was a pair of French jeans. Albuferon is a new drug for HCV & good data was presented today from an early clinical study in patients, my next report. Gilead reported new adefovir resistance data- 11% after 3 yrs, 18% after 4 yrs therapy.
"IDENIX REPORTS PRELIMINARY 24-WEEK PHASE IIA CLINICAL TRIAL DATA FOR VALOPICITABINE (NM283) IN COMBINATION WITH PEGYLATED INTERFERON FOR THE TREATMENT OF HEPATITIS C"
Patients receiving the combination treatment achieved a mean viral load reduction of 4.5 log10, or more than 99.99 percent, after 24 weeks of treatment
Paris, FRANCE; April 14, 2005 — Idenix Pharmaceuticals, Inc. (NASDAQ: IDIX), 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 naïve 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™ 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 TaqMan 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-Intron dose of 1.0 µg/kg is administered once a week starting on day 8. Enrolled patients are treatment naïve, 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), and eight out of nine patients achieved virus levels below 600 IU/mL, the Amplicor assay’s lower limit of quantification. Four of the nine patients achieved undetectable virus levels by real-time PCR by week 12 and maintained this response through week 24.
In the phase IIa clinical trial, tolerance for valopicitabine treatment continues to be satisfactory, with no serious adverse events. No discontinuations have resulted from valopicitabine-related adverse events.
"We are very encouraged by the 24-week antiviral effect reported in patients receiving the combination of valopicitabine and pegylated interferon even though this trial was designed as a drug-drug interaction trial and not to maximize the potential therapeutic response in patients," commented Nathaniel Brown, M.D., Idenix’s executive vice president, clinical development and chief medical officer. "We have designed the phase IIb trials to optimize potential outcomes of the combination treatment and we will be able to evaluate the full potential of valopicitabine from these trials."
Valopicitabine Clinical Development: In addition to the phase IIa trial in treatment naïve patients, Idenix is conducting a phase IIb clinical trial comparing the combination of valopicitabine plus Pegasys to the current standard of care in 171 HCV genotype 1 patients who have failed prior pegylated interferon plus ribavirin therapy. In this 24-week clinical trial, patients will receive valopicitabine monotherapy, valopicitabine plus Pegasys, or Pegasys plus ribavirin. This clinical trial is statistically powered to compare the two combination treatment regimens, and will further evaluate the safety of the full 800 mg/day dose of valopicitabine. The valopicitabine plus Pegasys regimen is divided into three dosing arms: 400 mg/day of valopicitabine plus Pegasys, 800 mg/day of valopicitabine plus Pegasys, and a titrating dose of valopicitabine up to 800 mg/day on day 8 plus Pegasys. Current enrollment in this trial is approximately 50 percent complete with 85 patients on treatment. Idenix expects to complete enrollment by June 2005.
About Valopicitabine (NM283): Valopicitabine (NM283) is a novel, oral nucleoside analog that was co-discovered by Idenix and the University of Cagliari through a cooperative laboratory agreement under the direction of Dr. Paolo LaColla, Director of the Department of Biomedical Sciences and Technologies of the University.
About Hepatitis C: There are approximately 170 million people worldwide with chronic HCV infection, of which approximately 2.7 million are in the United States. Chronic HCV infection accounts for 40 percent of end-stage cirrhosis, 60 percent of liver cancer and 30 to 40 percent of liver transplants in the United States and other industrialized countries. Responses to current treatment options are frequently inadequate due to the inability of some patients to tolerate these treatments and by their limited effectiveness, particularly in patients infected with HCV genotype 1. The genotype 1 strain of HCV is the most treatment-resistant HCV genotype and is estimated to cause more than 70 percent of the reported cases of hepatitis C in the U.S. and Japan, and more than 65 percent of the reported cases of hepatitis C in Western Europe.
About Idenix: Idenix Pharmaceuticals, Inc. is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral and other infectious diseases. Idenix’s current focus is on the treatment of infections caused by hepatitis B virus, hepatitis C virus and human immunodeficiency virus (HIV). Idenix’s headquarters are located in Cambridge, Massachusetts and it has drug discovery operations in Montpellier, France and Cagliari, Italy. For further information about Idenix, please refer to http://www.idenix.com.
Forward-looking Statements: This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Act of 1995. Statements in this press release other than those that are historical in nature are "forward-looking statements." Such forward looking statements, which include statements with respect to the potential therapeutic benefits and successful development of the company’s drug candidates are subject to numerous factors, risks and uncertainties that may cause actual events or results to differ materially from the company’s current expectations. These risks and uncertainties relate to the results of clinical trials and other studies with respect to the drug candidates that the company has under development; the timing and success of submission, acceptance and approval of regulatory filings; the company’s ability to obtain additional funding required to conduct its research, development and commercialization activities; and the company’s ability to obtain, maintain and enforce patent and other intellectual property protection for its drug candidates and its discoveries. These and other risks are described in greater detail under the caption "Factors that May Affect Future Results" in the company’s annual report on Form 10-K for the year ended December 31, 2004 and filed with the Securities and Exchange Commission and other filings that the company makes with the Securities and Exchange Commission.
All forward-looking statements reflect the company’s expectations only as of the date of this release and should not be relied upon as reflecting the company’s views, expectations or beliefs at any date subsequent to the date of this release. Idenix anticipates that subsequent events and developments may cause these views, expectations and beliefs to change. However, while Idenix may elect to update these About Valopicitabine (NM283): Valopicitabine (NM283) is a novel, oral nucleoside analog that was co-discovered by Idenix and the University of Cagliari through a cooperative laboratory agreement under the direction of Dr. Paolo LaColla, Director of the Department of Biomedical Sciences and Technologies of the University.
