Hospitalier Pitie Salpetriere Release: Clinical Benefits Of Retreatment With PegIntron And Rebetol Combination Therapy Demonstrated In Difficult-To-Treat Hepatitis C Patients

PARIS, April 18 /PRNewswire/ -- Interim results from a major ongoing clinical study showed that a significant portion of patients chronically infected with hepatitis C virus (HCV) who failed previous therapies achieved a sustained viral response (SVR) when retreated with weight-based PegIntron(R) (peginterferon alfa-2b) and Rebetol(R) (ribavirin) combination therapy. Results from the first treatment phase of the EPIC(3) (Evaluation of PegIntron in Control of Hepatitis C Cirrhosis) trial(1), a large multicenter global clinical study involving approximately 2,200 patients at approximately 140 sites worldwide, were presented yesterday in an oral presentation at the European Association for the Study of the Liver (EASL) 40th Annual Meeting.

Patients who were nonresponders or those that had relapsed after any previous interferon-based therapy received weight-based PegIntron (1.5 mcg/kg/wk) and Rebetol (800-1,400 mg/day) combination therapy for up to 48 weeks. Of the first 978 patients enrolled in the EPIC(3) trial, 21 percent achieved an SVR, defined as undetectable virus (HCV-RNA negative) six months after the end of therapy. This is nearly double the SVR rate of 12 percent in patients retreated with peginterferon alfa-2a and ribavirin reported in a similar patient population (HALT-C trial)(2).

"Patients who failed previous HCV therapy need viable treatment options," said Prof. Thierry Poynard, M.D., Hopital Pitie-Salpetriere, and a lead investigator of the EPIC(3) trial. "Our research demonstrates that this difficult-to-treat patient group can be successfully retreated with PegIntron and Rebetol combination therapy."

In addition to examining the ability of PegIntron and Rebetol to achieve SVR in patients who failed previous therapy, researchers also evaluated the ability of Early Virologic Response (EVR), defined as >2 log10 decrease or undetectable HCV-RNA at week 12, to predict the likelihood of achieving SVR in these patients. Of those patients who attained EVR, 36 percent achieved SVR: 57 percent of those with undetectable HCV-RNA at week 12 achieved SVR, but only 4 percent of those with detectable viral load at week 12. Patients who were nonresponders or relapsers with undetectable HCV-RNA at week 12 were equally like to achieve SVR (56 vs. 57 percent). Results of EPIC(3) showed that in addition to patients with undetectable HCV-RNA at week 12, retreatment also may be a good option for patients with other key factors affecting response:

* SVR was higher in patients with genotype 2 or 3 virus (56 percent) versus patients with genotype 1 virus (14 percent) (p<0.01); genotype 1 is the most difficult-to-treat form of hepatitis C. * SVR was higher in patients who had relapsed after previous therapy (41 percent) versus patients who were nonresponders (14 percent) (p<0.01). * SVR was higher in patients with F2/3 (mild-to-moderate) fibrosis (26 percent) versus patients with F4 (advanced) fibrosis (15 percent) (p<0.01).

"We continue to make advances in the treatment of hepatitis C and today have improved products and treatment regimens. However, this still remains a challenging disease to conquer," Poynard said. "We know that some HCV patients will not be able to clear the virus with the currently available therapies. In EPIC(3), we are researching ways to prevent liver disease progression in these patients using low-dose PegIntron maintenance therapy. Our goal is to keep these patients healthy until the next generation of HCV products become available."

The EPIC(3) Study

The EPIC(3) study is essentially three studies in one evaluating PegIntron and Rebetol combination therapy. The study involves: 1) a trial in patients who failed previous therapy with sustained virological response (SVR) as the clinical endpoint for patients with F2-4 fibrosis; 2) a trial to improve liver histology with long-term therapy in patients with F2-3 fibrosis; and 3) a trial to improve clinical endpoints in cirrhotic patients (both nonresponders and previously untreated patients).

The EPIC(3) study will involve approximately 2,200 patients with fibrosis (but not cirrhosis) in an initial treatment phase, and approximately 1,700 patients, who either did not respond to treatment in the first phase and/or have cirrhosis, in a second, long-term (three-to-five year) maintenance treatment phase.

Initial Treatment Phase: HCV patients with F 2-4 fibrosis (mild-to- advanced scarring but not cirrhosis) who did not respond or who relapsed after previous treatment with interferon therapy with or without ribavirin are retreated with weight-based PegIntron (1.5 mcg/kg/wk) and Rebetol (800-1,400 mg/day) combination therapy for 48 weeks.

Maintenance Treatment Phase: patients who either did not respond in the initial treatment phase and/or have cirrhosis will receive a weight-based low dose of PegIntron (0.5 mcg/kg/wk) as long-term maintenance therapy. The study will evaluate whether a maintenance dose of PegIntron monotherapy can delay or prevent life-threatening liver disease caused by the virus in patients with advanced disease.

The EPIC(3) study is sponsored by Schering-Plough Research Institute and is being conducted in the United States, Europe, Latin American and the Far East.

The 2,100-bed Groupe Hospitalier Pitie-Salpetriere is the largest hospital in France with 20 Research Units and serves more than 500,000 patients per year. Its faculty includes 110 full Professors of Medicine. In addition to serving the people of France, the hospital also is a teaching facility with 600 students from the Universite Paris VI.

References: (1) Poynard T, Schiff E, Terg R, Goncales F, Diago M, Reichen J, Moreno R, Bedossa P, Burroughs M, Albrecht J. Sustained Virologic Response (SVR) In the EPIC(3) Trial: Week Twelve Virology Predicts SVR in Previous Interferon/Ribavirin Treatment Failures Receiving PegIntron/Rebetol (PR) Weight Based Dosing (WBD). Oral presentation. Sunday, April 17: 40th Annual Meeting of the European Association for the Study of Liver (EASL), Paris, France, April 14-17, 2005. (2) DiBisceglie A, Division of Gastroenterogy and Hepatology, St Louis University School of Medicine, St Louis, MO. Results of HALT-C Trial; Digestive Disease Week 2003 Conference, Orlando, FL, USA, May 17-23, 2003.

Hospitalier Pitie Salpetriere

CONTACT: Professeur Thierry Poynard, Fax: +33-1-45-86-20-22,; or Molly Watson of Ritz Communications, +1-413-454-3926,Office: +1-413-568-5794

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