Study shows weight-based REBETOL dosing in combination with PEG-INTRON significantly improves ...

10/29/04



Study shows weight-based REBETOL dosing in combination with PEG-INTRON significantly improves viral clearance in African-American patients with most-difficult-to-treat form of hepatitis C

WIN-R study provides important insights on improving hepatitis C treatment among African-Americans

(BOSTON, Oct. 29, 2004) – Twice as many African-American patients infected with the most difficult-to-treat form of chronic hepatitis C successfully cleared the virus when given a weight-based dose of REBETOL® (ribavirin, USP) rather than a flat dose, in combination with PEG-INTRON® (peginterferon alfa-2b), according to data presented at a Presidential Plenary session at the 55th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) on Monday, November 1, at noon. The new findings, involving nearly 400 African-American patients from the large multicenter WIN-R study, are significant because African-Americans are known to have generally lower rates of response to hepatitis C therapy, and efforts are underway to improve outcomes for these patients.

"These results show that individualized therapy with weight-based ribavirin offers a significant advantage over a flat dose of ribavirin in the treatment of African-American patients chronically infected with hepatitis C genotype 1, the most difficult form of the virus to treat," said study principal investigator Ira M. Jacobson, M.D., Vincent Astor Professor of Clinical Medicine at Weill Cornell Medical College and chief of the division of gastroenterology and hepatology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City. "It's also important to note that in this study the overall safety of weight-based ribavirin dosing was similar to that of the flat 800 mg dose," he said.

The WIN-R (Weight-Based Dosing of PEG-INTRON and REBETOL ) study is the largest prospective clinical study in hepatitis C undertaken to date, involving approximately 4,900 patients from about 250 centers throughout the United States. The community-based study is evaluating the safety and efficacy of weight-based PEG-INTRON in combination with fixed or weight-based REBETOL in a diverse patient population, including the largest number of African-American patients in any study to date.

PEG-INTRON is indicated for use alone or in combination with REBETOL for the treatment of chronic hepatitis C in patients not previously treated with interferon alpha who have compensated liver disease and are at least 18 years of age. The recommended dose in the United States of this combination therapy is PEG-INTRON 1.5 mcg/kg/week by subcutaneous injection and REBETOL 800 mg/day taken orally for 48 weeks. Overall, approximately 50 to 60 percent of patients receiving this combination therapy regimen achieve a sustained virologic response (SVR). SVR is defined as the absence of detectable levels of the hepatitis C virus (HCV) six months following treatment and is considered the standard measure of efficacy. Numerous studies have shown that SVR rates among African-Americans are lower (19 to 26 percent) in response to current treatments.

"We know that HCV genotype and the dose and duration of therapy are critical factors for treatment success, but these factors alone do not seem to account for the lower responses seen in

African-American patients," Dr. Jacobson said. "The large amount of data in African-American patients generated by the WIN-R study add to our body of knowledge of how to best treat the disease, but it's important to do additional research to improve outcomes for these patients."

In the WIN-R study, patients were randomized to receive PEG-INTRON (1.5 mcg/kg/week) combined with REBETOL given as a flat dose (800 mg daily) or a weight-based dose (WBD) (800 mg, 1,000 mg, 1,200 mg or 1,400 mg daily for body weights of less than 65 kg, 65 to 85 kg, 86 to 105 kg, and 106 to 125 kg, respectively). The patients were treated for 48 weeks and followed for an additional 24 weeks.

In the AASLD presentation, investigators reported on findings in 387 African-American patients with chronic hepatitis C genotype 1. Of the 362 patients weighing 65 kg or more, significantly more in the WBD group achieved an SVR compared to those in the flat-dosed group: 21 percent vs. 10 percent (p=0.004). Relapse occurred in fewer patients in the WBD group: 22 percent compared to 31 percent. Among all 387 patients, the SVR rates for the WBD and flat-dosed groups were 19 percent and 11 percent, respectively (p=0.02). Anemia (hemoglobin less than 10 gm/dL) occurred in more patients in the WBD group than in the flat-dosed group (20 percent vs.15 percent), but overall safety and treatment discontinuations due to adverse events were similar for both groups.

WIN-R is an investigator-initiated study supported by Schering-Plough and monitored by Schering-Plough Research Institute as part of a post-marketing commitment to the U.S. Food and Drug Administration.

Collaborating with the study's principal investigator Dr. Jacobson was Dr. Robert S. Brown Jr., co-principal investigator of the study; associate professor of clinical medicine at

Columbia University College of Physicians and Surgeons; and chief of clinical hepatology, and medical director of the Center of Liver Disease and Transplantation at NewYork-Presbyterian Hospital/Columbia University Medical Center. Drs. Jacobson and Brown are also co-directors of NewYork-Presbyterian Healthcare System's Liver Clinical Trials Network (LCTN).

About Hepatitis C
Hepatitis C is the most common blood-borne infection in America. It affects approximately 4 million people, or about one in every 50 adults, including a disproportionately high percentage of African-Americans. Chronic hepatitis C can cause cirrhosis, liver failure, and liver cancer. It has been estimated that at least 20 percent of patients with chronic hepatitis C develop cirrhosis, and a smaller percentage of patients with chronic disease develop liver cancer. Patients with chronic hepatitis C and related cirrhosis are 100 times more likely to develop liver cancer than uninfected persons. About half of all cases of primary liver cancer in the developed world are caused by hepatitis C, and hepatitis-C-related liver disease is now the leading cause for liver transplants.

About NewYork-Presbyterian Hospital/Weill Cornell Medical Center
The NewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian Hospital and its academic partner Weill Cornell Medical College. NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory, and preventive care in all areas of medicine, and is committed to excellence in patient care, research, education, and community service.

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