Executive Summary

The sole pivotal study of Peg-Intron monotherapy in 1,219 adults with previously untreated chronic hepatitis C and compensated liver disease showed that once-weekly Peg-Intron is twice as active as Intron A injection three times weekly, the company reported May 1 at the Annual Meeting of the European Association for the Study of the Liver. The primary endpoint was sustained loss of HCV-RNA (SVR) 24 weeks following the end of therapy. Loss was 33% for Peg-Intron 0.5 ug/kg, 41% for Peg-Intron 1.0 ug/kg, 49% in Peg-Intron 1.5 ug/kg, and 24% for Intron A 3MU. "The rates of sustained virologic response achieved in this study were greatly influenced by genotype, and ranged from 11% for patients with genotype 1, the predominant genotype worldwide and the most difficult to treat, to 49% for patients with genotype 2 or 3, compared to 6% to 28% for Intron A," the company said. Peg-Intron, a longer-acting form of Intron A using PEG technology developed by Enzon, "was just as well tolerated" as Intron A, the firm said. The company submitted a BLA Dec. 23, 1999, for Peg-Intron for treatment of chronic hepatitis C. Preliminary results of a Phase II dose-ranging trial of Peg-Intron in combination with Rebetol (ribavirin) in 72 patients with chronic hepatitis C and compensated liver disease were also presented at the meeting. Patients were randomized to either Peg-Intron 0.35, 0.7 or 1.4 ug/kg once weekly alone or in combination with daily ribavirin (600, 800, or 1,000-1,200 mg) for 24 weeks, with 24 weeks follow-up. The company said that combination patients "achieved higher rates of sustained virologic response at 48 weeks compared to patients receiving the same doses of Peg-Intron alone." The European Committee for Proprietary Medicinal Products recommended April 18 that approval of the agent be restricted to use as monotherapy in hepatitis C patients who have failed or are intolerant to ribavirin in interferon-alpha/ribavirin combination therapy