15-country trial confirms Pegasys' superiority over lamivudine -

A new study shows that Pegasys provides a significantly greater proportion of patients with lasting remission compared to the current standard of care, lamivudine, in the treatment of chronic hepatitis B. The study was conducted in patients with 'e' antigen (HBeAg) positive hepatitis B - a subtype of the disease which affects the majority of hepatitis B patients worldwide. The results were presented today at the 55th Annual Meeting of the American Association for the Study of Liver Diseases in Boston, USA.

Six months after completing therapy, 32% of patients treated with Pegasys for 48 weeks achieved the primary endpoint of 'HBe' seroconversion compared with 19% treated with lamivudine, a nucleoside analogue. 'HBe' seroconversion is a marker for long-term remission of the disease. It is characterized by the loss of HB 'e' antigen (a protein indicating replication of the virus) and the development of antibodies against the virus. Importantly, another marker of disease remission, 'HBs' seroconversion, was only observed with Pegasys therapy in this study.* 'HBs' seroconversion is a very rare event which is as close to a cure as it is possible to get.

"These are really practice-changing results," said Dr George Lau, gastroenterologist at the Queen Mary Hospital, Hong Kong; Assistant Dean in the Department of Medicine at the University of Hong Kong and lead investigator of the trial. "There is now evidence from two trials in HBeAg-positive hepatitis B that Pegasys is more beneficial than conventional interferon1 or lamivudine, both of which are today considered the first-line treatments. In a disease that is next to impossible to eradicate, Pegasys has a very good ability to fight it."

"With the mounting evidence we have demonstrating the superiority of Pegasys to the most commonly used medications for chronic hepatitis B today, we feel confident that Pegasys will be adopted by physicians as a first-line treatment when it becomes available next year," said William M. Burns, Head of Pharmaceutical Division.

About chronic hepatitis B

Chronic hepatitis B is a major global healthcare problem affecting more than 350 million people and it is one of the principal causes of liver failure, cirrhosis, and liver cancer. Between one-quarter and one-third of people with chronic hepatitis B will go on to develop progressive liver disease; and approximately one million die annually, making it the 10th leading cause of death worldwide.

About the study

A total of 814 patients from 15 countries were enrolled in the study. Patients were treated for 48 weeks with Pegasys 180µg 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. Between 85% and 87% of patients enrolled in each treatment arm were Asian as HBeAg-positive disease is more prevalent in people of Asian descent.

Key findings

The study examined two primary and common endpoints of therapy that are indicators of a successful response to treatment: 'HBe' seroconversion and long-term reduction in viral load (HBV DNA levels).

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

-- 32% of patients treated with Pegasys achieved HBe seroconversion, compared to 19% of those treated with lamivudine. The addition of lamivudine to Pegasys did not improve the treatment outcome.

-- Significantly more patients treated with Pegasys achieved a reduction in HBV DNA levels to below 100,000 copies/ml compared to lamivudine alone (32% vs. 22% respectively). Again, the combination of Pegasys and lamivudine was not statistically different to Pegasys alone

-- The percentage of patients who normalised ALT (an enzyme that is marker of liver inflammation) levels was significantly higher with Pegasys (41%) versus lamivudine-treated patients (28%).

-- HBs seroconversion was reported in 16 patients treated with Pegasys (with or without lamivudine) and in none of the patients treated with lamivudine alone.

About Pegasys

Pegasys, a new generation hepatitis therapy that is different by design, has already become the worldwide market leader in hepatitis C. Roche filed Pegasys globally for a new indication to treat both HBeAg-positive and HBeAg-negative chronic hepatitis B in July. When approved, it will become the first pegylated interferon indicated for the treatment of chronic hepatitis B. The data for Pegasys in HBeAg-negative disease was published in the New England Journal of Medicine last month.2

Roche in hepatitis

Roche is committed to the viral hepatitis disease area, having introduced Roferon-A for hepatitis B and C, followed by Pegasys in hepatitis C and a full development program in hepatitis B which has now been completed. Roche has its own brand of ribavirin, COPEGUS, which is used in conjunction with Roferon A or Pegasys for HCV. In addition, Roche manufactures HBV and HCV diagnostic and monitoring systems: The COBAS AMPLICOR Test, and the AMPLICOR MONITOR Test, two testing systems used to detect the presence of, and quantity of, HBV DNA or HCV RNA in a person's blood.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world's leading research-intensive healthcare groups. Its core businesses are pharmaceuticals and diagnostics. As a supplier of innovative products and services for the prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is number one in the global diagnostics market, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2003, the Pharmaceuticals Division generated 19.8 billion Swiss francs in prescription drug sales, while the Diagnostics Division posted sales of 7.4 billion Swiss francs. Roche employs roughly 65,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai.

* HBs seroconversion is characterized by loss of the HB 's' antigen and development of antibodies against that part of the virus.

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References:

1. Cooksley WG, Piratvisuth T, Lee SD, et al. Peginterferon alpha-2a (40 kDa): an advance in the treatment of hepatitis B e antigen-positive chronic hepatitis B. J Viral Hepat 2003;10:298-305.

2. Marcellin P, Lau GK, Bonino F, et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med 2004;351:1206-17.

Further information:
WHO Factsheet Hepatitis B

View drug information on Pegasys.