Summarizes NM 283 Data Presented at the American Association for the Study of
Liver Diseases (AASLD)
CAMBRIDGE, MA, Nov. 1 /PRNewswire-FirstCall/ -- 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 mug/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. 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 drug candidates that the company has under development and the
company's drug discovery, research and clinical development and regulatory
approval processes, 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
dependence on its collaboration with Novartis Pharma AG, the company's ability
to obtain additional funding required to conduct its research, development and
commercialization activities, the ability of the company to attract and retain
qualified personnel 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 in the
"Risk Factors" section of the company's quarterly report on Form 10-Q for the
quarter ended June 30, 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 forward-looking statements at some point in the
future, it specifically disclaims any obligation to do so.
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SOURCE Idenix Pharmaceuticals, Inc.
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Related links:
http://www.idenix.com
CONTACT:
Media: Teri Dahlman, +1-617-995-9905 or
Investors: Amy Sullivan, +1-617-995-9838, both of Idenix
Pharmaceuticals
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