Valopicitabine Dosed in Combination with Pegylated Interferon Alfa-2a (Pegasys)

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Valopicitabine Dosed in Combination with Pegylated Interferon Alfa-2a

(Pegasys) Leads to Rapid Virologic Response in 93 percent of Genotype

1 Hepatitis C Patients

Idenix Pharmaceuticals announced on January 9, 2005 partial 4-week

data from an ongoing phase IIb clinical trial demonstrating that

treatment with valopicitabine combined with pegylated interferon alfa-

2a (Pegasys) resulted in rapid and marked reduction in virus levels

in treatment-naive genotype 1 hepatitis C patients. Valopicitabine is

an experimental, oral nucleoside analog in development for the

treatment of chronic hepatitis C.

Following are excerpts from the Idenix statement on the new partial 4-

week data from the valopicitabine study:

The mean reduction in HCV levels in this trial was greater than or

equal to 4 log10, or 99.99 percent, after 4 weeks of treatment among

patients in the two dose groups that began on Day 1 with 800 mg doses

of valopicitabine. This trial is almost fully enrolled, with a target

enrollment of 175 patients at more than 20 medical centers in the

U.S.

These partial data will be presented at the 24th Annual JP

Healthcare Conference on Wednesday, January 11 at 2:00 p.m. (PST).

The conference is taking place in San Francisco, January 9-12, 2006.

" We are quite encouraged by the virologic responses demonstrated to

date with these four-week data and believe that valopicitabine

combined with pegylated interferon has the potential to substantially

improve treatment efficacy compared to current therapy for chronic

hepatitis C patients, " said Jean-Pierre Sommadossi, Ph.D., chairman

and chief executive officer of Idenix. " We look forward to presenting

additional data from this phase IIb clinical trial in the spring and

initiating a phase III clinical trial in this patient population in

the second half of 2006. "

This ongoing 48-week phase IIb clinical trial in treatment-naive

patients includes the following five randomized treatment arms, all

involving dosing regimens of valopicitabine, administered once-daily,

in combination with pegylated interferon alfa-2a (Pegasys) 180

micrograms per week:

(1) Pegylated interferon beginning on Day 8 plus valopicitabine

ramping from 400 mg to 800 mg beginning at Day 29;

(2) Valopicitabine 200 mg beginning on Day 1 plus pegylated

interferon beginning on Day 8;

(3) Valopicitabine ramping from 400 mg to 800 mg beginning on Day 1

plus pegylated interferon beginning on Day 8;

(4) Valopicitabine 800 mg beginning on Day 1 plus pegylated

interferon beginning on Day 8; and

(5) Valopicitabine 800 mg plus pegylated interferon, both beginning

on Day 1.

The partial 4-week data demonstrated that the four treatment arms

that included valopicitabine in combination with pegylated interferon

during the first four weeks (arms B-E) all produced proportionally

greater suppression of serum HCV RNA as compared to the arm that

included pegylated interferon alone for the first four weeks (arm A).

At Week 4, mean HCV RNA reductions were 4.00 log10, 4.17 log10, 3.50

log10 and 3.09 log10, respectively, for arm E (15 patients), arm D

(14 patients), arm C (18 patients) and arm B (17 patients).

In comparison, patients in the arm receiving pegylated interferon

alone for the first 4 weeks (arm A, 19 patients) achieved a mean HCV

RNA reduction of 2.00 log10 . The mean HCV RNA reduction for the two

800 mg dose valopicitabine arms (arms D and E) was significantly

greater than that of the pegylated interferon alone arm (arm A)

(p<0.01).

The addition of 800 mg of valopicitabine to pegylated interferon (arm

D) led to viral clearance (PCR- negativity) in 50 percent of

patients, compared to 11 percent in arm A, at Week 4.

Rapid virologic response (RVR), or a greater than or equal to 2 log10

reduction in viral load by Week 4, was achieved in 93 percent of

patients in the two 800 mg dose valopicitabine arms (arms D and E),

indicative of a degree of virologic response which, in treatment

naive patients, is thought to correlate with potentially sustained

viral clearance post treatment.

Preliminary data from the first 4 weeks of treatment indicate

valopicitabine continues to demonstrate adequate tolerability when

administered in combination with pegylated interferon. Of the 150

patients enrolled in the trial to date, ten patients discontinued

treatment by week four; nine discontinuations were due to adverse

events (including 1 SAE of severe dehydration), and one for

logistical reasons.

About Valopicitabine

Valopicitabine, which is administered orally once a day, is intended

to block HCV replication by specifically inhibiting the HCV RNA

polymerase, the enzyme that makes new copies of HCV viral chromosome

inside infected cells.

Data from the phase I clinical trial sponsored by Idenix demonstrated

that valopicitabine is active in patients infected with the genotype

1 strain of HCV, the strain that infects the majority of patients in

North America, Europe, and Japan.

The ongoing phase II clinical trials are designed to evaluate the

combination of valopicitabine and pegylated interferon in hepatitis C

genotype 1 patients who previously failed to respond to antiviral

treatment (nonresponders), as well as in genotype 1 patients who have

not been treated previously.

Preliminary results from these phase II clinical trials to date have

demonstrated that the antiviral effect of valopicitabine is enhanced

when this agent is used in combination with pegylated interferon.

About Hepatitis C

Hepatitis C is an infectious liver disease caused by the hepatitis C

virus. The World Health Organization estimates that 170 million

individuals worldwide carry chronic HCV infection, with 3 to 4

million new infections occurring globally each year. It is the most

common chronic blood-borne infection in the United States with 2.7

million chronically infected.

Chronic HCV infection causes inflammation of the liver, which may

cause progressive liver damage that can lead to cirrhosis (liver

scarring), hepatocellular carcinoma (liver cancer), liver failure,

and death. Patients infected with HCV genotype 1 are difficult to

treat, with half or fewer such patients achieving sustained responses

to current standard treatment regimens involving a combination of

pegylated interferon plus ribavirin.

These " non-responders " or treatment-refractory patients comprise a

growing patient population, who have no proven alternative treatments

available and who are at risk for progressive HCV-associated liver

disease.

As the prevalence of severe liver disease attributable to chronic

hepatitis C rises, deaths due to complications from hepatitis C

infection, currently 8,000 to 10,000 per year in the United States,

are expected to increase dramatically over the next 15 to 20 years.

(1)

For information about Idenix Pharmaceuticals, please visit http://