Idenix
Pharmaceuticals, Inc. (Nasdaq: IDIX) today announced results from a phase
II study designed to evaluate triple combination therapy, consisting of
valopicitabine (NM283), Idenix's lead drug candidate for the treatment of
hepatitis C, pegylated interferon and ribavirin compared to pegylated
interferon and ribavirin, the current standard of care, in patients
infected with the genotype-1 strain of the hepatitis C virus (HCV). This
study demonstrated no pharmacokinetic or pharmacodynamic drug-drug
interaction between valopicitabine and ribavirin. The triple combination
showed consistently higher rates of HCV PCR-negativity, defined as serum
HCV RNA levels below 20 copies/mL, compared to the standard of care at
every point analyzed in this study. Additionally, the tolerability of the
triple combination was satisfactory, with only three discontinuations from
the study.
"I am very encouraged to observe this degree of viral clearance coupled
with a very low rate of discontinuations in patients treated with the
triple combination of valopicitabine, pegylated-interferon and ribavirin in
this study," said Dr. Fred Poordad, Chief of Hepatology and Liver
Transplantation, Cedars Sinai Medical Center, and an investigator in this
study. "These data represent an important achievement in the development of
novel HCV combination therapy."
Study Design and Results
The three-arm, partially blinded, randomized study enrolled 117
treatment- naive, HCV genotype-1 infected patients at approximately 20
centers in the United States. Patients in arm A (n=39) received 200 mg/day
of valopicitabine and pegylated interferon alpha 2a; patients in arm B
(n=39) received 200 mg/day of valopicitabine, weight-based dosing of
ribavirin, and pegylated interferon alpha 2a; and patients in arm C (n=39)
received placebo, weight- based dosing of ribavirin and pegylated
interferon alpha 2a. For all patients in this study there was a seven day
lead-in period, where patients received either valopicitabine or placebo
alone; the additional components of each arm's therapeutic regimen were
administered beginning on day eight.
The primary endpoint of the study was to assess pharmacokinetic and
pharmacodynamic drug-drug interaction between valopicitabine and ribavirin
after 36 days of treatment. Drug levels for both NM107 (the active form of
valopicitabine) and ribavirin when administered alone or together were
within the range of 80 to 125 percent, indicating the lack of an
interaction. At day 36, 23 percent of patients treated with triple
combination therapy (arm B) were HCV PCR-negative per protocol, compared to
11 percent of patients treated with the standard of care (arm C) and 14
percent of patients treated with valopicitabine and pegylated interferon
(arm A). These findings demonstrated no pharmacokinetic or pharmacodynamic
drug-drug interaction between valopicitabine and ribavirin.
The key secondary endpoints for the study were antiviral activity,
safety and tolerability at 12 weeks. Of patients that completed 12 weeks of
therapy, 72.2 percent of patients treated with triple combination therapy
(arm B) achieved HCV PCR-negativity, compared to 61.5 percent of patients
treated with the standard of care (arm C). There were three
discontinuations from the study, all due to adverse events (AEs), one of
which was attributed by the clinical investigator to valopicitabine-related
gastrointestinal toxicity. The two other AEs, including a serious adverse
event (SAE), were attributed by the clinical investigators to pegylated
interferon or pegylated interferon/ribavirin. All of the discontinuations
occurred in the triple combination arm (arm B).
At the end of 12 weeks, patients were permitted to roll over to
pegylated interferon plus ribavirin for up to 48 weeks of total treatment;
all eligible patients elected to do so.
"These results support our hypothesis that valopicitabine can be
administered in combination with pegylated interferon and ribavirin," said
Douglas Mayers, M.D., executive vice president and chief medical officer of
Idenix Pharmaceuticals. "We are very pleased with the viral kinetics and
HCV RNA clearance rates observed in patients treated with triple
combination therapy in this study and look forward to further development
of this combination."
About Valopicitabine
Valopicitabine is an investigational nucleoside polymerase inhibitor
being evaluated in ongoing clinical trials for the treatment of hepatitis
C. The most common adverse events reported in valopicitabine clinical
trials to date include nausea, vomiting, fatigue, diarrhea, headache,
flu-like symptoms and depression. Idenix is developing valopicitabine in
collaboration with Novartis Pharma AG.
About Hepatitis C
HCV infection is the most common chronic blood-borne infection in the
United States.(1) The Centers for Disease Control and Prevention estimates
that 4 million Americans have been infected with HCV, and 2.7 million of
these carry chronic HCV infections.(2) Hepatitis C-related liver failure is
the most common indication for liver transplantation in the United
States.(2) As the prevalence of severe liver disease attributable to
hepatitis C rises, deaths due to complications from hepatitis C infection,
currently 8,000 to 10,000 per year in the United States, are increasing and
are expected to triple by 2010.(3)
About Idenix
Idenix Pharmaceuticals, Inc., headquartered in Cambridge,
Massachusetts, is a biopharmaceutical company engaged in the discovery,
development and commercialization 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 HIV. For
further information about Idenix, please refer to idenix.
Forward-looking Statements
This press release contains "forward-looking statements" within the
meaning of The Private Securities Litigation Reform Act of 1995. Such
forward- looking statements can be identified by the use of forward-looking
terminology such as "will," "can be," "expect," "anticipates," "advance,"
"significant achievement," "pending," "encouraging," "believe," or similar
expressions and implied statements with respect to the regulatory success
of valopicitabine or the Idenix clinical development program in hepatitis
C, or any potential pipeline candidates and expectations with respect to
the size of the market for Hepatitis C. Such forward-looking statements
involve known and unknown risks, uncertainties and other factors that may
cause actual results to be materially different from any future results,
performance or achievements expressed or implied by such statements. In
particular, management's expectations could be affected by unexpected
regulatory actions or delays; results of clinical trials, including
additional data relating to the ongoing or future clinical trials
evaluating its product candidates; the company's ability to obtain
additional funding required to conduct its research, development and
commercialization activities; the company's dependence on its collaboration
with Novartis Pharma AG; the ability of the company to attract and retain
qualified personnel; competition in general; the company's ability to
obtain, maintain and enforce patent and other intellectual property
protection for its product candidates and its discoveries and the Company's
ability to accurately assess the market. These and other risks which may
impact management's expectations are described in greater detail under the
caption "Risk Factors" in the company's annual report on Form 10-K for the
year ended December 31, 2006 and filed with the Securities and Exchange
Commission, the Company's Quarterly Report on Form 10-Q for the quarter
ended March 31, 2007 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.
References
(1) Center For Disease Control National Prevention Strategy.
(2) Center for Disease Control. Hepatitis C Fact Sheet accessed online
at cdc/ncidod/diseases/hepatitis/c/fact.htm.
(3) Davis, G. et al., Projecting Future Complications of Chronic
Hepatitis C in the United States. Liver Transplantation, April 2003.
Idenix Pharmaceuticals, Inc.
idenix