Valeant to Present 24-week Results from DIRECT Trial of Infergen

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Valeant to Present 24-week Results from DIRECT Trial of Infergen

Valeant to Present 24-Week Results from DIRECT Trial of Infergen

Earlier this month, Valeant Pharmaceuticals announced that

researchers would present data from the DIRECT trial -- studying

consensus interferon (Infergen) in chronic hepatitis C patients who

did not respond to prior treatment with pegylated interferon plus

ribavirin -- at the 57th AASLD meeting, taking place this weekend in

Boston.

Following are excerpts form the Valeant press release:

Valeant Pharmaceuticals Previews 24-Week Results of DIRECT Trial for

Infergen

48-Week Results to Be Presented at the American Association for the

Study of Liver Diseases Conference in October

COSTA MESA, Calif. -- Valeant Pharmaceuticals International

(NYSE:VRX) today previewed its 24-week data from the Infergen

(Consensus Interferon) DIRECT trial through an abstract submitted to

and accepted by the American Association for the Study of Liver

Diseases (AASLD). Additional data, including 48 week data, will be

presented as a late-breaker poster at the upcoming AASLD meeting in

Boston on October 30, 2006.

The DIRECT trial is evaluating the daily use of Infergen in

combination with ribavirin for the treatment of hepatitis C in

patients who were non-responsive to previous pegylated interferon and

ribavirin therapy. The screening criteria for this trial were very

strict, which resulted in more than 75 percent of patients having

evidence of advanced fibrosis/cirrhosis (stage 3 and 4). Patients

also were especially heavy, with an average weight of 89 kg (196

lbs.) and also had been off therapy (washed out) for a median of 395

days in the 9 mcg group and 492 days in the 15 mcg group. No patients

in the study received growth factors for treatment of neutropenia or

anemia.

Early virologic response rates (>/= 2 log10 decline in HCV RNA or

undetectable HCV RNA) in the trial for the Infergen 9 mcg and 15 mcg

groups were 46 percent and 54 percent, respectively (TMA assay). The

percent of patients who were virus negative at week 24 were 14

percent and 20 percent for the Infergen 9 mcg and 15 mcg groups,

respectively (TMA assay). Response rates at 24 weeks using the bDNA

assay were 26 percent and 32 percent for the Infergen 9 mcg and 15

mcg groups, respectively.

Non-cirrhotic patients, including patients with bridging fibrosis,

receiving Infergen 15 µg daily experienced 25 percent viral

negativity at 24 weeks (36 percent by bDNA). Of the non-cirrhotic

patients who maintained at least 80 percent of their Infergen and

ribavirin doses, the response rate was 33 percent (47 percent by

bDNA).

The washout period (days from completion of at least 12 weeks of

compliant pegylated interferon and ribavirin therapy to the first

dose of Infergen in the DIRECT trial) had a significant impact on

viral response as well. Patients receiving Infergen 15 mcg daily with

a washout period less than the 492 median days were twice as likely

to be virus free at week 24 (26 percent vs. 13 percent by TMA). The

company plans to perform further analyses of these data and will

present them at the AASLD meeting, including the 48-week results in

the analysis as well.

" These early results from the DIRECT trial are promising. The high

percentage of patients with advanced disease and the long washout

period make this a challenging population to treat. These patients

had not previously responded to pegylated interferon and ribavirin,

and it is encouraging that companies are developing new treatment

options with the potential to help many of these patients achieve a

sustained virologic response, " commented Bruce R. Bacon, MD, the

DIRECT trial lead investigator and Director of the Division of

Gastroenterology and Hepatology at Saint Louis University.

" To date, there is no approved therapy to treat the growing number of

pegylated interferon and ribavirin non-responders. Pending the final

sustained virologic response rates, Valeant plans to seek FDA

approval for the daily use of Infergen and ribavirin for the

treatment of pegylated interferon non-responders, " said Wesley P.

Wheeler, Valeant's President of North America and Global Product

Development.

About DIRECT

The DIRECT (Daily-Dose Consensus Interferon and Ribavirin: Efficacy

of Combined Therapy) trial is a Phase 3 open-label multi-center U.S.-

based study enrolling patients who were previous non-responders and

compliant with at least 12 weeks of pegylated interferon and

ribavirin therapy. The 343 genotype non-2, 3 patients enrolled were

randomized to receive either Infergen 9 mcg/day plus ribavirin (1.0-

1.2 g/day) or Infergen 15 mcg/day plus ribavirin (1.0-1.2 g/day) for

48 weeks. The patients enrolled were required to have less than a 2

log10 decline in viral load while undergoing at least 12 weeks of

previous pegylated interferon and ribavirin therapy or have

detectable HCV RNA at the end of treatment, after completing at least

24 weeks of pegylated interferon and ribavirin.

Patient demographics in the trial include patients with a mean age of

50 years, 70 percent male, 67 percent high viral load (> 2 million

copies/ml), 92 percent genotype 1, a mean weight of 89 kg, 20 percent

African Americans, 65 percent Caucasians, and 77 percent with

evidence of liver disease, including bridging fibrosis or cirrhosis

on biopsy. The median washout period was 395 days for the Infergen 9

mcg cohort and 492 days for the Infergen 15 mcg group.

The most common adverse events were fatigue, flu like symptoms,

nausea, headache, and insomnia and were similar between groups. The

percent of patients modifying their Infergen dose due to adverse

events were 24 percent in the Infergen 9 mcg cohort and 39 percent in

the Infergen 15 µg group. Neutropenia was the most comment adverse

event leading to dose modification and occurred in 12 percent in the

Infergen 9 mcg cohort and 21 percent in the Infergen 15 mcg group.

Growth factors were not used in the study.

About Infergen

Infergen or consensus interferon is a bio-optimized, selective, and

highly potent type 1 interferon alpha originally developed by Amgen

and launched in the United States in 1997. It is currently indicated

as monotherapy for the treatment of adult patients suffering from

chronic hepatitis C viral infections with compensated liver disease

and is dosed three times per week. Infergen is the only interferon

with data in the label regarding use in patients following relapse or

non-response to certain previous treatments.

Infergen is being studied in ongoing clinical trials to evaluate its

potential for daily use with ribavirin. Enrollment in the Phase 3

IHRC-001 (DIRECT) trial was completed in mid-2005 with 514 patients

at 40 sites in the United States. The DIRECT trial, which should be

completed in 2007, is evaluating the safety and efficacy of both 9

mcg and 15 mcg doses of daily Infergen in combination with ribavirin

in non-responders.