New study to evaluate Pegasys and Copegus to treat hepatitis C in liver transplant patients

Roche has initiated a new study to evaluate treatment strategies to reduce post-transplant recurrence of hepatitis C infection with the most prescribed hepatitis C treatment combination in the U.S., Pegasys (peginterferon alfa-2a) and Copegus (ribavirin, USP). In the United States, hepatitis C is the leading cause of liver transplantation.

The new study will compare prophylactic combination therapy with Pegasys and Copegus (to prevent the virus from attacking the transplanted liver) with the same combination therapy administered once hepatitis C infection recurs histologically in the transplanted liver.

"Hepatitis C is one of the greatest challenges we face in liver transplantation today," said Juan Carlos Lopez-Talavera, M.D., Ph.D., Senior Medical Director, Roche. "Approximately 30 percent of all Americans who receive liver transplants each year have chronic hepatitis C. We know that without treatment, hepatitis C almost always begins to attack the transplanted liver in patients with the disease."

Hepatitis C, a blood-borne infectious disease of the liver, is transmitted through body fluids, primarily blood or blood products, and by sharing needles. Hepatitis C chronically infects an estimated 2.7 million Americans and 170 million people worldwide.

"There are many questions to be answered such as how safe and effective is hepatitis C combination therapy for patients who have received a liver transplant, and when is treatment most effective. It is our hope that this study will help determine the best strategy for managing hepatitis C in patients who have received a liver transplant," said Michael Charlton, M.D., Associate Professor of Medicine and Director of Transplant Research, Mayo Clinic College of Medicine.

The study will enroll approximately 300 patients and include 28 trial sites throughout the United States. Patients in the study will be randomized into two arms between the 10th and 16th week post liver transplantation. Study participants who have not experienced liver damage post-transplantion, will receive 135mcg/week of Pegasys via subcutaneous injection for the first 4 weeks, which will then increase to 180mcg/week for the next 44 weeks. Patients will also receive between 400 mg/day to 1200 mg/day (escalated) of Copegus. Participants in the observation arm of the study will not receive treatment unless histological recurrence is demonstrated. These patients will then receive Pegasys and Copegus treatment with similar dosing as the prophylactic arm.

All patients must be over 18 years of age and have had a cadaveric liver transplantation due to hepatitis C between 10 to 16 weeks prior to initiation of treatment. Patients with a pre-transplant diagnosis of hepatocellular

carcinoma (HCC), or liver cancer, may be enrolled provided there is no evidence that the cancer has spread, tumor is solitary and less than 5cm or there are up to three tumors less than 3cm. Patients who received multiple organs, or who have hepatitis A or hepatitis B infection, human immunodeficiency virus (HIV), pre-existing severe depression or other psychiatric disease, significant cardiac disease, renal disease, seizure disorders, or severe retinopathy are excluded.

All patients will be evaluated at 24 months to determine if they have experienced hepatitis C recurrence measured by fibrosis stage 2 or greater and/or inflammation grade 3 or greater.