Major PEGASYS Trial in Chronic Hepatitis B Patients Published in New England Journal of Medicine

BASEL, Switzerland -- The New England Journal of Medicine today published the results of a key international trial(1) that clearly establishes the superior efficacy and safety of PEGASYS(R) (peginterferon alfa-2a) in patients with hepatitis B e antigen (HBeAg) negative chronic hepatitis B over lamivudine, the current standard of care. Significantly the authors conclude that PEGASYS "constitutes a therapeutic advance over current treatments" in this difficult-to-treat and advanced stage of the disease and support its use as first-line therapy.(2)

The results showed that patients receiving PEGASYS alone had significantly higher rates of response, sustained for 24 weeks after cessation of therapy, than patients receiving lamivudine, a nucleoside analogue, and that the addition of lamivudine to PEGASYS did not improve post-therapy response rates. This is the largest single study of HBeAg-negative patients.

"We need new effective medications like PEGASYS to treat HBeAg-negative chronic hepatitis B which is increasing in prevalence throughout the world," said Professor Patrick Marcellin, hepatologist at the Hôpital Beaujon, Clichy, France and the lead author of the study. "Available treatments have shortcomings. They generate a response during treatment but relapse rates are high once therapy is stopped so the rates of sustained response are poor. As a result, it has become common practice to have patients continue on nucleoside or nucleotide analogues indefinitely and we know that this strategy is associated with the risk of resistance and unknown long-term safety implications."

About the study

A total of 537 patients from 13 countries were enrolled in the study(3). Patients were treated for 48 weeks with PEGASYS 180 mg once weekly plus placebo, lamivudine 100 mg once daily, or a combination of PEGASYS and lamivudine. Treatment response was assessed following a 24-week treatment-free follow-up period.

Key findings

The study examined two primary and common endpoints of therapy which are indicators of liver damage and viral suppression: normalization of alanine aminotransferase (ALT) levels and suppression of HBV DNA levels. In addition, the investigators assessed the proportion of patients with HBsAg loss and HBsAg seroconversion (disappearance of the hepatitis B virus surface antigen (HBsAg) and the presence of antibodies to HBsAg). "HBsAg loss or seroconversion after therapy is considered the ultimate therapeutic goal of anti-HBV therapy, since it is associated with positive long-term clinical outcomes," the authors note.

At week 72 (24 weeks after the completion of therapy), it was found that:

- 43 percent of patients treated with PEGASYS monotherapy reduced their hepatitis B viral DNA to less than 20,000 copies per ml compared to 29 percent of those treated with lamivudine. The addition of lamivudine to PEGASYS did not improve the treatment outcome.

- The percentage of patients with normalized alanine aminotransferase levels was significantly higher with PEGASYS monotherapy: 59 percent versus 44 percent of lamivudine-treated patients. The combination of PEGASYS and lamivudine (60 percent) was not statistically different to PEGASYS alone.

- Loss of HBsAg was reported in 12 patients treated with PEGASYS (with or without lamivudine) and in none of the patients treated with lamivudine alone. HBsAg seroconversion subsequently occurred in eight of these patients. The authors note that "HBsAg loss or seroconversion was not reported in several clinical trials of lamivudine or adefovir in patients with HBeAg-negative chronic hepatitis B."

The authors conclude that the ability of PEGASYS "to improve and sustain biochemical, virologic, and HBsAg response rates constitutes a therapeutic advance over current treatments, which are associated with poor rates of sustained response after the cessation of therapy. Our data demonstrate the possibility of achieving HBsAg loss or seroconversion in patients with HBeAg-negative chronic hepatitis B with the use of peginterferon alfa-2a and therefore support the use of this agent as a first-line therapy for HBeAg-negative chronic hepatitis B."

(1) Marcellin, Patrick et al. Peginterferon Alfa-2a Alone, Lamivudine Alone, and the Two in Combination in Patients with HBeAg-Negative Chronic Hepatitis B. New England Journal of Medicine 2004; 351: 32-43.

(2) PEGASYS is currently not indicated for the treatment of chronic HBV. Roche filed globally for an indication in HBV in July and it is anticipated that the product will be approved in 2005.

(3) Countries that participated included: Canada, China, France, Germany, Greece, Italy, New Zealand, Poland, Spain, Switzerland, Taiwan, Thailand and Turkey.

Source: Roche Pharmaceuticals