SAN FRANCISCO, CA -- (MARKET WIRE) -- 11/14/05 -- Final results of the WIN-R trial,(1) the largest hepatitis C study conducted in U.S. patients, showed that weight-based REBETOL® (ribavirin, USP) in combination therapy with PEG-INTRON® (peginterferon alfa-2b) achieved significantly higher rates of sustained virologic response (SVR)(2) and lower rates of relapse compared to the combination therapy using a flat dose of ribavirin. The study also showed that, for patients infected with hepatitis C virus (HCV) genotype 2 or 3, a shorter, 24-week course of therapy was as effective as the standard 48-week course, with better tolerability.

These results from WIN-R (Weight-Based Dosing of PEG-INTRON and REBETOL), a community-based access trial involving more than 4,900 patients at 225 centers across the United States, were reported in an oral presentation today at the 56th annual meeting of the American Association for the Study of Liver Diseases (AASLD).

"These findings help further define optimal therapy for U.S. hepatitis C patients treated in real-world community settings," said principal investigator Ira M. Jacobson, M.D., Vincent Astor Professor of Clinical Medicine at Weill Medical College of Cornell University and chief of the division of gastroenterology and hepatology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City.

Treating U.S. hepatitis C patients can be especially challenging as they tend to have disease characteristics that are associated with poor response to treatment, including high prevalence of HCV genotype 1, the most difficult type of the virus to treat; high viral load; and advanced liver fibrosis. Other factors such as age, high body weight and African-American ethnicity also have been shown to be associated with poor response.

"Our findings showed that the weight-based dosed combination therapy significantly increased efficacy compared to the flat-dosed ribavirin regimen, especially in more difficult-to-treat patient groups, such as patients with genotype 1 and African-American patients. This confirms what many treating physicians have come to know in their everyday practice and experience," Jacobson said. "Importantly, sustained virologic response rates in this community-based U.S. study were consistent with those seen in the U.S. cohorts of the earlier pivotal studies for the two approved peginterferon combination therapies."(3,4)

Study Design

In the WIN-R study, 4,913 patients were randomized to receive weight-based PEG-INTRON (1.5 mcg/kg weekly) in combination with REBETOL given either as a flat dose (800 mg daily) or a weight-based dose (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, or 106 to 125 kg, respectively). Patients were treated for 48 weeks (genotype 1) or 24 weeks (genotype 2 or 3). Patients in the treatment arms were evenly matched for gender, age, body weight, genotype, viral load and stage of liver fibrosis.

Key Results

A challenge with conducting large community-based HCV studies such as WIN-R, as opposed to registration trials with their more intensive monitoring capabilities, is the tendency for a high rate of patients to miss their follow-up viral testing (PCR) visit 24 weeks after treatment ends due to the limited ability of many sites to conduct rigorous monitoring of patients once they have received their final treatment dose. In the WIN-R study, 13.1 percent (164/1,256) of patients in the weight-based dose group and 13.7 percent (163/1,193) of patients in the fixed-dose group who were responders at the end of treatment were lost to follow up and subsequently counted as treatment failures under a strict intent-to-treat (ITT) analysis.

Nonetheless, the WIN-R study showed significantly better outcomes for the weight-based combination regimen as compared to the flat-dosed ribavirin regimen, including:

--  Significantly higher SVR overall (44.3 percent vs. 40.6 percent,
    p=0.01, ITT) and for patients with genotype 1 (34 percent vs. 29 percent,
    p=0.004, ITT). These SVR rates are consistent with those seen in the U.S.
    cohorts of the earlier pivotal studies for the two approved peginterferon
    combination therapies.(3,4)

--  Using an estimated SVR analysis, based on results for patients who had
    undetectable virus at the end of treatment and were subsequently lost to
    follow up, SVR was 53 percent vs. 48 percent (p=0.008), respectively, for
    the weight-based vs. flat-dosed ribavirin groups.

--  Consistent SVR rates were seen across all weight groups for patients
    in the weight-based dosed regimen compared to the flat-dosed ribavirin
    regimen where SVR rates declined in the higher weight groups, ranging from
    52 percent to 34 percent. Consistent with other U.S. studies, patient
    weight tended to be high in the WIN-R study, with 45 percent of patients
    weighing 86 kg (189 lbs) or more.

--  For patients with HCV genotype 2 or 3 virus, a 24-week course of the
    combination therapy was as effective as 48 weeks, with better tolerability.
    In the weight-based dose arms, SVR was 68 percent for the 24-week course
    compared to 60 percent for the 48-week course, with the lower percentage
    attributable to more missing follow-up data.

--  Lower rates of relapse were seen for patients receiving the weight-
    based combination therapy compared to the flat-dosed ribavirin regimen, 15
    percent vs. 19 percent overall, and 23 percent vs. 29 percent for patients
    with HCV genotype 1. Relapse is defined as patients with undetectable virus
    levels at the end of treatment who subsequently had detectable virus at 24
    weeks post-treatment.

--  Although there was a higher rate of anemia (hemoglobin < 10 gm/dl) in
    the weight-based dosing group and more dose reductions (29 percent vs. 23
    percent), no difference was seen in the rate of occurrence of serious
    adverse events between the two groups (12 percent vs. 11 percent) and there
    were similar rates of discontinuations for adverse events (15 percent vs.
    14 percent).
    

WIN-R Study

Serving with Dr. Jacobson as co-principal investigator of the WIN-R study is Dr. Robert S. Brown Jr., 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).

Dr. Jacobson also is medical director of the Center for the Study of Hepatitis C, a unique interdisciplinary center established jointly by The Rockefeller University, NewYork-Presbyterian Hospital and Weill Cornell Medical College in New York City.

WIN-R is an investigator-initiated clinical study supported by Schering-Plough Corporation and monitored by Schering-Plough Research Institute as part of a post-marketing commitment to the U.S. Food and Drug Administration (FDA). PEG-INTRON and REBETOL are registered trademarks of Schering-Plough.

About Hepatitis C

Hepatitis C is the most common blood-borne infection in America, affecting approximately 4 million people or about one in every 50 adults. 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.(5) 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.(6)

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 in-patient, ambulatory, and preventive care in all areas of medicine, and is committed to excellence in patient care, research, education, and community service.

References

1. Jacobson I, Brown Jr. R, Freilich B, Afdahl N, Kwo P, Santoro J, Becker S, Wakil A, Pound D, Godofsky E, Strauss R, Bernstein D, Flamm S, Bala N, Araya V, Davis M, Monsour H, Vierling J, Regenstein F, Balan V, Dragutsky M, Epstein M,. Herring RW, Rubin R, Galler G, Pauly MP, Griffel LH, Brass CA, the WIN-R Study Group. Weight based ribavirin dosing (WBD) increases sustained viral response (SVR) in patients with chronic hepatitis C (CHC): final results of the WIN-R study, a U.S. community-based trial. Oral presentation at: 56th Annual Meeting of the American Association for the Study of Liver Diseases, San Francisco, CA, Nov 11-15, 2005.

2. Sustained virologic response (SVR) is defined as undetectable virus (HCV-RNA) levels in the blood at 6 months after the end of therapy.

3. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65.

4. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002 Sep 26;347(13):975-82.

5. Ince N, Wands JR. The increasing incidence of hepatocellular carcinoma. N Engl J Med 1999 March 11;340:10.

6. Centers for Disease Control and Prevention. Recommendations for prevention and treatment of hepatitis C virus (HCV) and HCV-related chronic disease. MMWR Weekly Report 1998 Oct. 16;1.

Contact:
Andrea Ziltzer
Chandler Chicco Agency
(914) 522-4804
(212) 229-8433
Email Contact

Jonathan Weil
NewYork-Presbyterian/Weill Cornell
(212) 821-0560
Email Contact