Rebetol® Resulted in Low Relapse Rates in Chronic Hepatitis C Patients

FDA Approves Label Revisions Recommending New Weight-Based Dosing Regimen

KENILWORTH, N.J. -- Schering-Plough Corporation reported that the U.S. Food and Drug Administration (FDA) has approved label revisions for PEGINTRON™ (peginterferon alfa-2b) and REBETOL® (ribavirin, USP) combination therapy for chronic hepatitis C, recommending weight-based dosing of REBETOL (800-1400 mg daily) based on patient body weight. The revised label also recommends a shorter, 24-week course of the combination therapy for patients with chronic hepatitis C virus (HCV) genotype 2 or 3.

The revisions represent the first FDA approval of a 1,400 mg ribavirin dose and the widest ribavirin dosing range approved for use in combination with peginterferon for treating chronic hepatitis C in patients with compensated liver disease.

The label changes are based on the results of the WIN-R trial,¹ the largest U.S. hepatitis C study, conducted in more than 4,900 patients. The study showed that PEGINTRON (1.5 mcg/kg once weekly) and REBETOL (800-1,400 mg daily based on patient body weight) resulted in a significantly higher sustained virologic response (SVR)² compared to PEGINTRON in combination with a flat 800 mg daily dose of REBETOL, the previously labeled dose. Importantly, the study reported low relapse rates consistent with other PEGINTRON studies.^3,4

"PEGINTRON and weight-based ribavirin was significantly more effective than flat-dosed ribavirin, especially in genotype 1 patients, and provided consistent efficacy across all weight groups," said WIN-R principal investigator Ira M. Jacobson, MD, Vincent Astor Professor of Clinical Medicine at Weill Medical College of Cornell University and chief of the division of gastroenterology and hepatology at New York Presbyterian Hospital/Weill Cornell Medical Center in New York City.

"It is reassuring to now have a validated, FDA-approved regimen that will allow us to use a novel 1,400 mg ribavirin dose in our highest-weight hepatitis C patients, who previously were among the most difficult to treat successfully," said Robert S. Brown Jr., MD, MPH, co-principal investigator of the WIN-R study, and chief of the division of abdominal organ transplantation, New York-Presbyterian Hospital/Columbia University Medical Center.

In WIN-R (Weight-Based Dosing of PEGINTRON and REBETOL), SVR rates remained consistent with increased body weight for patients receiving weight-based REBETOL, but SVR decreased as body weight increased for patients receiving a flat-dose. The study also showed that for patients with HCV genotype 2 or 3, 24 weeks of weight-based dosed combination therapy was as effective as 48 weeks. For patients with genotype 1, 48 weeks of PEGINTRON and REBETOL combination therapy is recommended.

In the WIN-R study, there was a higher rate of anemia among patients in the weight-based dosing group compared to the flat-dosing group. The majority of these cases were mild and responded to dose reductions. There was no difference seen in the rate of serious adverse events between the two groups and there were similar rates of discontinuations for adverse events.

"We are very pleased with the FDA approval of these label revisions. Schering-Plough has long championed an individualized approach to hepatitis C treatment with weight-based PEGINTRON and REBETOL combination therapy to help optimize outcomes for patients," said Robert J. Spiegel, MD, chief medical officer and senior vice president, Schering-Plough Research Institute. "Further underscoring this individualized approach, we recently reported results of another larger study in more than 3,000 U.S. patients, known as the IDEAL study,⁴ which also confirmed the efficacy and low relapse rate of PEGINTRON in combination with weight-based REBETOL."

WIN-R was an investigator-initiated clinical study supported by Schering-Plough Corporation as part of a post-marketing commitment to the FDA.

References
(1) Jacobson IM, et al. Peginterferon alfa-2b and Weight-Based or Flat-Dose Ribavirin in Chronic Hepatitis C Patients: A Randomized Trial. Hepatology 2007; 46:971-981.
(2) p=0.01, primary efficacy comparison (based on data from subjects weighing 65 kg or higher at baseline and utilizing a logistic regression analysis that includes treatment [weight-based dose or flat dose], genotype and presence/absence of advanced fibrosis, in the model).
(3) Manns MP, et al. Peginterferon alfa-2b plus Ribavirin Compared with Interferon alfa-2b plus Ribavirin for Initial Treatment of Chronic Hepatitis C: A Randomized Trial. Lancet 2001;358:958-965.
(4) The IDEAL (Individualized Dosing Efficacy vs. Flat Dosing to Assess optimal pegylated interferon therapy) study. Schering-Plough press release, Jan. 14, 2008.

Source: Schering-Plough Corporation

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