The US Food and Drug Administration (FDA) has approved label revisions for Schering-Plough Corporation's 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 1400 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, the largest US hepatitis C study, conducted in more than 4,900 patients. The study showed that Pegintron (1.5 mcg/kg once weekly) and Rebetol (800-1400 mg daily based on patient body weight) resulted in a significantly higher sustained virologic response (SVR) compared to Pegintron in combination with a flat 800 mg daily dose of Rebetol, the previously labelled dose. Importantly, the study reported low relapse rates consistent with other Pegintron studies.
"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, 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 New York Presbyterian Hospital/Weill Cornell Medical Centre in New York City.
"It is reassuring to now have a validated, FDA-approved regimen that will allow us to use a novel 1400 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., M.D., M.P.H., co-principal investigator of the WIN-R study, and chief of the division of abdominal organ transplantation, New York-Presbyterian Hospital/Columbia University Medical Centre.
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 anaemia 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, M.D., 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 US patients, known as the IDEAL study, 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.
In the United States, Pegintron is indicated for use alone or with ribavirin for the treatment of chronic hepatitis C in patients with compensated liver disease who have not been previously treated with interferon alpha and who are at least 18 years of age.