Idenix Presents New Data for NM 283 for the Treatment of Hepatitis C
Cambridge, MA, November 1, 2004
Summarizes NM 283 Data Presented at the American Association for the Study of Liver Diseases (AASLD)
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, is today presenting new data for its drug candidate, NM 283, an antiviral agent for the treatment of
hepatitis C virus (HCV), which is currently in a phase IIa clinical trial.
New data for NM 283 are being presented at AASLD's 55th Annual Meeting in Boston by Dr. Nezam Afdhal of Harvard Medical School.
In this late-breaker oral presentation today at 5:15 p.m., Dr. Afdhal will discuss final data from the NM 283 phase I clinical trial including the
800 mg/day monotherapy cohort that demonstrated a 1.2 log10, or 94 percent, mean viral load (HCV RNA) reduction from baseline in patients with chronic
hepatitis C after 15 days of treatment.
Dr. Afdhal will also review interim 28-day data for 19 patients enrolled in an ongoing phase IIa clinical trial evaluating the combination of
NM 283 and pegylated-interferon. These interim results demonstrate that the 12 patients receiving the combination therapy achieved a mean viral load reduction
of 2.7 log10, or 99.8 percent, after 28 days of treatment. These preliminary HCV RNA responses from the phase IIa clinical trial appear more consistent
across the treated patient population and greater than results from other studies that reported data for 4 weeks of treatment with current standard therapy
(pegylated-interferons and ribavirin) in HCV-1 patients. To date, NM 283 has demonstrated a satisfactory safety profile with no treatment-related
discontinuations in either clinical trial. Both clinical trials include patients infected with chronic hepatitis C genotype 1, a difficult to
treat strain of the virus, which is the predominant HCV strain in the U.S., Europe and Japan.
"Although we have seen improvements in hepatitis C therapy during the past few years, there is still a
tremendous need for further treatment advances in efficacy, safety and tolerability particularly for patients who have
HCV genotype 1 and for patients who have failed interferon-based therapies," said Nezam Afdhal, M.D., a principal investigator in both NM 283
trials, Chief of Hepatology at Beth Israel Deaconess Medical Center in Boston and Associate Professor at Harvard Medical School. Dr. Afdhal continued,
"Data from these clinical trials are encouraging and suggest that NM 283 may prove to be a potentially new treatment option for these patients."
NM 283 - Phase I
The double-blind, randomized phase I dose escalation clinical trial was designed to evaluate the safety, pharmacokinetics and antiviral activity of NM 283 during 15 days of treatment with a 2-week follow-up period. All patients were chronically infected with the genotype 1 strain of HCV (HCV-1) and either had previously failed various interferon-based therapies (87%) or were previously untreated (13%).
The design of the phase I clinical trial included five once-daily dosing cohorts, 50, 100, 200, 400 and 800 mg, and one twice-daily dosing cohort of 200 mg. Two additional cohorts explored dose-titration methods to optimize gastrointestinal tolerance of higher daily doses. Each cohort included 12 patients, randomized so that 10 patients received NM 283 and 2 patients received placebo. Final data included 95 patients comprising eight dose groups of which 79 patients received assigned doses of NM 283 and 16 received placebo.
The final data from the phase I clinical trial indicate a dose-related, consistent viral load reduction after 15 days treatment with NM 283. Patients receiving 800 mg/day of NM 283 throughout the 15-day treatment period, the highest overall dose exposure, achieved a mean viral load reduction of 94 percent, or 1.2 log10. Transient, generally mild gastrointestinal side effects, consisting of nausea and, occasionally, vomiting, were observed in some patients. However, these side effects were never treatment limiting and all affected patients completed treatment uninterrupted. No serious adverse events, pattern of lab abnormalities, or dose-limiting toxicities were observed.
NM 283 - Phase IIa
A phase IIa clinical trial for NM 283 is currently ongoing, and is designed to assess the safety, antiviral activity and pharmacokinetics of the combination of NM 283 and pegylated interferon compared to NM 283 alone. This clinical trial, evaluating 30 previously untreated patients, was originally designed to include a 28-day treatment period. By protocol amendment, the treatment period has been extended to 3 months. Key entry criteria for this clinical trial include patients with HCV genotype 1, baseline viral load greater than 5 log10 copies/ml and alanine aminotransferase (ALT) levels less than 5 times the upper limit of normal. In this phase IIa clinical trial, patients are being randomized to one of two treatment arms so that 12 patients will receive NM 283 monotherapy and 18 patients will receive NM 283 plus pegylated interferon. In the combination treatment arm, patients receive a once-daily titrating dose of NM 283 beginning with 400 mg/day, then reaching 800 mg/day at day 8 and continuing with the 800 mg/day dose through the end of the treatment period. A 1.0 µg/kg dose of pegylated-interferon is administered on day 8 and every 7th day thereafter throughout the treatment period.
To date, 19 patients have been enrolled in the ongoing phase IIa study, with 7 patients randomized to the NM 283 monotherapy arm and 12 patients to the combination treatment arm. The interim data demonstrate marked, consistent, and rapid reductions in serum virus levels (HCV RNA levels) among the 12 patients receiving the combination treatment (NM 283 plus pegylated-interferon). Patients receiving the combination treatment achieved a mean viral load (HCV RNA) reduction of 2.7 log10 copies/mL through week 4, representing a 99.8 percent reduction in virus load in the first 4 weeks of treatment. Results for the combination regimen also show an enhanced antiviral effect compared to the NM 283 monotherapy arm. This result is consistent with data from preclinical laboratory studies, which suggested a synergistic antiviral effect for the combination of NM 283 plus interferon-alpha.
Of the 12 patients receiving combination treatment evaluated to date, 9 patients, or 75 percent, experienced early virologic response (EVR) at 28 days. In this therapeutic field, EVR is defined as a decrease in serum HCV RNA of greater than or equal to 2 log10 copies/mL. EVR is also demonstrated by a reduction of HCV RNA to levels undetectable by a highly sensitive polymerase chain reaction (PCR) assay. Scientists studying antiviral treatments, including treatments consisting of interferon plus ribavirin, have reported that the achievement of EVR by week 12 of treatment correlates with an improved chance of sustained viral clearance.
"The consistent antiviral effects observed with NM 283 in the completed phase I trial, in a population of patients comprised of both previously untreated patients and interferon non-responders, together with the early data from the phase IIa clinical trial, support continued and expanded clinical testing of NM 283 in combination with pegylated interferon," said Dr. Nathaniel A. Brown, executive vice president, clinical research, and chief medical officer of Idenix Pharmaceuticals. "While these results are promising, we look forward to evaluating the combination of NM 283 and pegylated-interferon for longer treatment durations in the extended phase IIa trial as well as a phase IIb trial."
Next Steps
Idenix plans to begin a phase IIb clinical trial for NM 283 by year-end 2004. This 6-month trial is expected to enroll approximately 165 HCV genotype 1 patients who have previously failed at least 3 months' treatment with current standard therapy (pegylated interferon plus ribavirin). This phase IIb trial is designed as a head-to-head study of the combination of NM 283 and pegylated interferon compared to the standard treatment regimen of pegylated interferon plus ribavirin. This phase IIb clinical trial will also include a monotherapy arm of NM 283. Idenix expects to complete the phase IIa and phase IIb trials for NM 283 in 2005.
About NM 283
NM 283 is an oral, novel, 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. After absorption, NM 283 is metabolized to a form that inhibits the HCV RNA polymerase. NM 283 has also demonstrated inhibition of HCV genotype 1 replication in chronically infected chimpanzees.
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. Currently available treatment options are frequently limited due to the ability of patients to tolerate such treatments and by the treatment regimens' 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% of the reported cases of hepatitis C in western Europe.
About Idenix
Idenix Pharmaceuticals, Inc. (NASDAQ: IDIX) 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.