Posted: 13-Jun-2007 << BACK
Valopicitabine Combined with Standard of Care Cleared Hepatitis C Virus in 72% of Patients Who Completed 12 Weeks of Treatment in a Phase II Trial - PRNewswire -
Idenix Pharmaceuticals, Inc. 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.
