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Phase 3 Studies Initiated for Boceprevir in Previously Untreated Hepatitis C Patients

KENILWORTH, N.J., May 21 /PRNewswire-FirstCall/ -- Schering-Plough Corporation (NYSE:SGP) , a leader in hepatitis research, today announced that it is initiating two large Phase III studies of boceprevir, its investigational oral hepatitis C protease inhibitor, in patients chronically infected with hepatitis C virus (HCV) genotype 1. One study will be in previously untreated (naive) patients and the other in patients who failed prior treatment (relapsers and nonresponders), an area of great unmet medical need. The two randomized, double-blind, placebo-controlled studies will evaluate the efficacy of boceprevir in combination with Peg Intron (peginterferon alfa-2b) and Rebetol(R) (ribavirin, USP) compared to standard of care with Peg Intron and Rebetol alone. The Company said the two pivotal studies will run concurrently and are projected to enroll a total of more than 1,400 patients at U.S. and international sites.

"We are excited to advance to Phase III clinical studies with boceprevir in combination with Peg Intron and Rebetol," said Fred Poordad, M.D., chief of hepatology in the division of gastroenterology at Cedars-Sinai Medical Center, associate professor of medicine at the David Geffen School of Medicine, University of California, Los Angeles (UCLA), and co-principal investigator of the Phase III study in naive patients. "These studies are designed to demonstrate that this combination therapy has the potential to benefit a broad range of patients by significantly increasing sustained response rates with a potentially shorter course of treatment."

In both Phase III clinical studies, patients will receive 4 weeks of treatment with Peg Intron and Rebetol prior to the addition of boceprevir. The rationale for this novel treatment paradigm is based on the fact that both Peg Intron and Rebetol reach steady-state concentrations by week 4, so patients have the protease inhibitor added at a time when the backbone drug levels have been optimized. In addition, the patient's immune system will have been activated and primed by Peg Intron at the time that boceprevir is added to the regimen. This approach may minimize the period of time when there is a "functional monotherapy" with a direct antiviral, and may help reduce the likelihood for the development of resistance by identifying patients who are responders to interferon and ribavirin prior to their receiving a protease inhibitor.

Pivotal Study in Previously Untreated (Naive) Patients The primary objective of this pivotal study, known as HCV SPRINT-2 (HCV Serine Protease Inhibitor Therapy-2), is to evaluate the efficacy of 28- and 48-week regimens of boceprevir (800 mg TID) in combination with Peg Intron (1.5 mcg/kg/week) and Rebetol (600-1400 mg/day) compared to a control of Peg Intron and Rebetol alone for 48 weeks in previously untreated (naive) adult patients with chronic HCV genotype 1. The study is projected to enroll a total of more than 1,000 patients, including a minimum of 150 African-American/Black patients.

In this study, in the 28-week treatment arm, rapid viral response (RVR) criteria at 4 weeks of boceprevir treatment (treatment week 8) will be used to determine which boceprevir patients can stop all treatment at 28 weeks. Patients in the 28-week boceprevir arm who achieve RVR, defined as undetectable virus (HCV-RNA) in plasma at week 4 of boceprevir treatment, will stop all treatment at week 28. Patients who do not meet the RVR criteria will stop boceprevir treatment at week 28 and continue Peg Intron and Rebetol alone for an additional 20 weeks, for a total treatment duration of 48 weeks. In the 48-week treatment arm, patients will receive Peg Intron and Rebetol plus boceprevir for a total treatment duration of 48 weeks. Patients in any arm of this study with detectable virus at week 24 will be considered treatment failures and will discontinue treatment.

The primary efficacy endpoint of the study is sustained virologic response (SVR).(1) Secondary efficacy endpoints include early virologic response in patients who achieve SVR. The study will be stratified by HCV genotype 1 subtype 1a versus 1b, and baseline viral load.

Professor Jean-Pierre Bronowicki, M.D., Ph.D., department of hepato-gastroenterology, University Hospital of Nancy, France, and Jonathan McCone, M.D., director, Mount Vernon Endoscopy Center, Alexandria, Va., are the other co-principal investigators of this study.

Pivotal Study in Patients Who Failed Prior Treatment
The primary objective of this pivotal study, known as HCV RESPOND-2 (Retreatment with HCV Serine Protease Inhibitor Boceprevir and Peg Intron/Rebetol) is to evaluate the efficacy of 36- and 48-week regimens of boceprevir (800 mg TID) in combination with Peg Intron (1.5 mcg/kg/week) and Rebetol (600-1400 mg/day) compared to a control of Peg Intron and Rebetol alone for 48 weeks in adult patients with chronic HCV genotype 1 who failed prior treatment with peginterferon and ribavirin combination therapy. The study is projected to enroll a total of 375 patients.

This study will enroll treatment-failure patients who have documented previous interferon responsiveness by achieving at least a 2 log decrease in viral load by week 12 of peginterferon and ribavirin therapy (nonresponders) or who were viral negative at end of peginterferon and ribavirin therapy, but did not obtain a sustained virologic response (relapsers). 'Null' responders -- those patients who do not meet the aforementioned criteria -- will not be enrolled in this study.

In this study, in the 36-week treatment arm, RVR criteria at 4 weeks of boceprevir treatment (treatment week 8) will be used to determine which boceprevir patients can stop all treatment at 36 weeks. Patients in the 36-week boceprevir arm who achieve RVR, defined as undetectable virus (HCV-RNA) in plasma at week 4 of boceprevir treatment, will stop all treatment at week 36. Patients who do not meet the RVR criteria will stop boceprevir treatment at week 36 and continue on Peg Intron and Rebetol alone for an additional 12 weeks, for a total treatment duration of 48 weeks. In the 48-week treatment arm, patients will receive Peg Intron and Rebetol plus boceprevir for a total treatment duration of 48 weeks. Patients in any arm of the study with detectable virus at week 12 will be considered treatment failures and will discontinue treatment.

The primary efficacy endpoint of the study is SVR.(1) Secondary efficacy endpoints include early virologic response in patients who achieve SVR. The study will be stratified by response to prior peginterferon and ribavirin therapy -- patients who achieved undetectable HCV-RNA (relapsers) versus those who did not (nonresponders) -- and by HCV genotype 1 subtype 1a versus 1b.

Source: Schering-Plough Corporation

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