BASEL, Switzerland, April 26 /PRNewswire/ --
- No Nucleoside/Nucleotide Analogue Treatments Have Shown Similar Results
New data revealed today show that a significant number of patients with chronic hepatitis B virus infection who received PEGASYS(R) (peginterferon alfa-2a) treatment achieved clearance of a blood antigen known as hepatitis B s-antigen (HBsAg) (1). Clearance of this marker is associated with favourable clinical outcomes, and is as close to a cure as possible in this disease (1-4). HBsAg clearance shows that an individual's own immune system is able to control the infection. None of the nucleoside/nucleotide analogue treatments for hepatitis B virus (HBV) have shown such a result.
The clinical improvements associated with s antigen clearance include a decreased rate of cirrhosis, a markedly decreased rate of liver cancer, and an increase in life expectancy (2-4).
These new data were presented at the European Association for the Study of the Liver (EASL) congress today in Milan, Italy. The data show that four years after the completion of a one-year treatment course with Pegasys, 11% of patients achieved this positive outcome, compared to only 2% of patients who received lamivudine, a commonly-used treatment for HBV. The response of patients taking lamivudine was similar to rates of spontaneous clearance of this marker for HBV (0.1 percent to 0.8 percent per year) (5,6).
Remarkably, the number of patients achieving s-antigen clearance increased each year even after Pegasys treatment was stopped, rising from 3% at year one, 6% at year two, 8% at year three and finally, to 11% at year four. The long-term benefits of treatment with Pegasys are thought to be due to the persistence of its immune system-stimulating effects. Unlike nucleoside/nucleotide analogue treatments for HBV, such as lamivudine, Pegasys works by fighting the disease in two ways: by boosting the immune system and at the same time, directly attacking the virus. Nucleoside/nucleotide analogues have a direct antiviral effect only, so the disease tends to come back in patients taking these medications when treatment has stopped (7-9). Because of this risk, these types of medicines usually require long-term or life-long treatment (7, 10, 11).
"These results with Pegasys in the treatment of HBV are unprecedented, because they show for the first time that patients treated with a pegylated interferon can achieve the best possible outcome following a 1-year course of treatment - HBsAg clearance," said Dr Patrick Marcellin, Professor of Hepatology at the University of Paris and Head of the Viral Hepatitis Research Unit in Hôpital Beaujon, Clichy, France. "These data appear to offer real hope of long-term freedom from this disease, and further bolster the case for using Pegasys as a first line treatment in patients with e-antigen negative chronic hepatitis B."
More About the Study
The data are from an international pivotal study of Pegasys which enrolled followed 537 e antigen-negative hepatitis B patients from 54 centres. It compared the efficacy of 48 weeks treatment with Pegasys 180 mcg, Pegasys 180 mcg plus lamivudine 100 mg, or lamivudine 100 mg alone. Initial results, published in the New England Journal of Medicine, showed superior efficacy for Pegasys compared to lamivudine -- as measured by HBV suppression and ALT normalization -- six months after the end of treatment (12).
The results reported at EASL, at 4 years post-treatment, are collected from centres which agreed to enter the long-term follow-up portion of the study (315 patients from 42 centres in all three arms). Data from both Pegasys treatment arms was combined for the analysis of response. In addition to the superior rates of s-antigen clearance among patients taking Pegasys, significantly more patients maintained suppression of HBV below 400 copies/ml compared to lamivudine (17% vs. 7%, respectively; p=0.042), and more patients had normal ALT levels (27% vs. 18%, respectively).
Notes for Editors
About Chronic Hepatitis B
Chronic hepatitis B is a serious global healthcare problem that affects more than 350 million people worldwide. It is one of the principal causes of chronic liver disease, cirrhosis, and primary liver cancer. Approximately one million people die from chronic hepatitis B annually, making it the tenth leading cause of death worldwide. For those chronically infected, the immediate aim of treatment is remission of liver disease to prevent progression to cirrhosis, liver failure, and primary liver cancer.
Pegasys in Hepatitis B
Pegasys is the only pegylated interferon to be approved for the treatment of chronic hepatitis B in over 60 countries. It is approved in the EU, the US and the People's Republic of China, among others.
Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world's biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is the world leader in in-vitro diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolic disorders and diseases of the central nervous system. In 2007 sales by the Pharmaceuticals Division totalled 36.8 billion Swiss francs, and the Diagnostics Division posted sales of 9.3 billion Swiss francs. Roche has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invested over 8 billion Swiss francs in R&D in 2007. Worldwide, the Group employs about 79,000 people. Additional information is available on the Internet at http://www.roche.com.
1. Marcellin P, Piratvisuth T, Brunetto M, et al. Virological and biochemical response in patients with HBeAg-negative chronic hepatitis B treated with peginterferon alfa-2a (40KD) with or without lamivudine: results of 4-year follow-up. Abstract presented at 43rd Annual Meeting of the European Association for the Study of the Liver (EASL); 26 April 2008; Milan, Italy.
2. Fattovich G, Giustina G, Sanchez-Tapias J, et al. Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to interferon alpha therapy and disease prognosis. European Concerted Action on Viral Hepatitis (EUROHEP). Am J Gastroenterol 1998;93:859-60.
3. Chen YC, Sheen IS, Chu CM, Liaw YF. Prognosis following spontaneous HBsAg seroclearance in chronic hepatitis B patients with or without concurrent infection. Gastroenterology 2002;123:1084-9.
4. Moucari R, Korevaar A, Asselah T, et al. High Rates of HBsAg Seroconversion in Chronic Hepatitis B Patients Responding to Interferon Therapy: a Long-term Follow-up Study. Abstract 991 presented at AASLD, Boston, USA 2-6 November 2007.
5. Wu TT, Hsu HC, Chen DS, et al. Clearance of hepatitis B surface antigen (HBsAg) after surgical resection of hepatocellular carcinoma. J Hepatol 1987;4:45-51.
6. Liaw Y-F, Pao C-C, Chu C-M, et al. Changes of serum hepatitis B virus DNA in two types of clinical events preceding spontaneous hepatitis B e antigen seroconversion in chronic type B hepatitis. Hepatology 1987;7:1-3.
7. Song BC, Suh DJ, Lee HC, et al. Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea. Hepatology 2000;32:803-6.
8. Chien RN, Yeh CT, Tsai SL, et al. Determinants for sustained HBeAg response to lamivudine therapy. Hepatology 2003;38:1267-73.
9. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. N Engl J Med 2005;352(26):2673-81.
10. Leung NW, Lai CL, Chang TT, et al. Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapy. Hepatology 2001;33(6):1527-32.
11. Marcellin P, Chang TT, Lim SG, et al. Long-term efficacy and safety of adefovir dipivoxil (ADV) 10 mg in HBeAg+ chronic hepatitis B (CHB) patients: increasing serologic, virologic and biochemical response over time. Hepatology 2004;40:655A.
12. Marcellin P, Lau GKK, Bonino F, et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. New Engl J Med 2004; 351: 1206-17.
Contact: Mike Nelson, Roche, +41-(79)-572-5165; Michelle Marchione, Axon Communications, +44(0)208-439-9449