SCH 503034 is being evaluated in a large Phase II study in combination with peginterferon alfa-2b (PegIntron) for the treatment of patients chronically infected with hepatitis C virus (HCV) genotype 1 who were nonresponders to peginterferon and ribavirin combination therapy. 

The company also reported that with the completion of enrollment of the original protocol doses (100, 200, 400 mg TID), it continues to explore a full range of dosing options for SCH 503034.  As such, the ongoing Phase II study has been expanded to include an additional treatment arm with SCH 503034 (800 mg TID) in combination with PEG-INTRON for 24 weeks.  This arm will enroll up to an additional 65 patients. 

In all, the ongoing Phase II study will enroll a total of approximately 350 patients at centers in the United States and Europe, making it the largest clinical study to date with an HCV protease inhibitor.

“SCH 503034 is one of the most advanced investigational agents in this new class of drugs that target key HCV proteins necessary for viral replication,” said Robert J. Spiegel, M.D., chief medical officer and senior vice president, Schering-Plough Research Institute.  “This promising oral antiviral agent has the potential to greatly improve treatment for all hepatitis C patients, and may lead to future regimens that are more effective, better tolerated and shorter in duration.”

The primary objective of the ongoing Phase II study is to determine the safe and effective dose range of SCH 503034 in combination with PegIntron in the HCV genotype 1 nonresponder patient population.  Secondary objectives are to explore the effect of ribavirin as a component of the therapeutic regimen and duration of therapy (24 vs. 48 weeks). 

The current standard of care in treating chronic hepatitis C is the combination of peginterferon and ribavirin. HCV genotype 1 is the most common form of the virus worldwide and is considered the most difficult to treat successfully. 

Currently, no alternative therapy has been shown effective for the large number of patients who failed previous therapies, representing an area of great unmet medical need.  Chronic hepatitis C affects more than 10 million people in major world markets and is the leading cause of chronic liver disease and reason for liver transplantation.

Future Studies with SCH 503034

Schering-Plough is undertaking a large, fully integrated clinical development program for SCH 503034 with the goal of developing new strategies for improving treatment outcomes for patients with hepatitis C, including nonresponders to standard therapy and previously untreated (naive) patients. 

This is particularly critical for patient populations with difficult-to-treat forms of the disease that are resistant to current therapies.  Specific subgroups of patients, for example, African-Americans, patients who are cirrhotic, patients co-infected with HIV and liver transplant recipients, are known to have different virologic responses and safety profiles when treated for hepatitis C with current interferon-based regimens. 

Schering-Plough is committed to evaluating SCH 503034 in these patient populations in future larger Phase III clinical studies or in separate trials focused on specific patient populations, as appropriate. 

Safety and Tolerability

In Phase I studies, SCH 503034 was shown to be safe and well tolerated at all dose levels evaluated, with no dose-related increase in the frequency of adverse events.  In a monotherapy study, adverse events with SCH 503034 were mild or moderate and similar to placebo.  The most frequently reported adverse event was headache.  In a combination study with PEG-INTRON, adverse events also were mild or moderate, with the adverse events being similar for the combination to those for  PegIntron alone, except for a slight increase in the incidence of headache. 

Clinical laboratory values such as bilirubin, creatinine and PPT were similar to placebo in the monotherapy study and to PegIntron  in the combination study.  Both Phase I clinical studies included ECG monitoring and no clinically significant changes in ECG were seen.

04/28/06

Reference
Schering-Plough. Schering Plough Provides Update on Oral HCV Protease Inhibitor SCH 50334 Clincial Development Program for Hepatitis C. Press Release. April 20, 2006.