Gilead Sciences recently announced its five-year data from the open-label phase of two pivotal phase III clinical trials (Studies 102 and 103) evaluating the efficacy of Viread (tenofovir disoproxil fumarate) for the treatment of chronic hepatitis B virus (HBV) infection among primarily treatment-naïve  patients.  

The initial results showed that Viread maintains a long-term viral suppression of HBV and is associated with a reduction in liver fibrosis and a reversal of cirrhosis. Among patients in both studies, the majority i.e. about 88 per cent experienced an improvement in  overall liver histology.  Together, these two studies represents one of the largest datasets evaluating the
impact of an oral antiviral therapy on histologic changes and showing a reduction in liver fibrosis.  

These  findings were presented at the 62 annual meeting of the American  Association for the Study of Liver Diseases (The Liver Meeting 2011) in San Francisco. “We have long theorised that long-term antiviral therapy can not only help chronic hepatitis B patients  to achieve and maintain virologic suppression, but also help to improve clinical outcomes, including a reduction in the risk of fibrosis or cirrhosis,” informed Patrick Marcellin, medical director of Hôpital Beaujon in Clichy, France, INSERM CRB3 and University of Paris Denis Diderot, and the principal investigator of Study 102.

He further said that these results represent an important  advance in HBV therapy because they elucidate Viread’s potential to reduce or reverse signs of liver damage in patients with chronic hepatitis B.

Studies 102 and 103 were designed to compare Viread to Hepsera  (adefovir dipivoxil) in a blinded manner over 48 weeks, among both HBeAg-negative (Study 102) and HBeAg-positive (Study 103) patients with compensated liver disease. Patients originally randomised to Hepsera in both studies were switched to open-label Viread at 48 weeks  and patients randomised to Viread continued on open-label Viread.

The data show that majority of patients who received Viread continuously for 240 weeks experienced sustained suppression of HBV DNA (viral load) levels in the blood below 400 copies/mL (83 per cent and 64 per cent for studies 102 and 103, respectively).  Patients who were randomised to Hepsera and rolled over to Viread at week 48 and received Viread for a subsequent 192 weeks also maintained viral suppression (84 percent and 66 percent for Studies 102 and 103, respectively).

Notably, among the 331 patients who had paired biopsies at both baseline and week 240, 292 (88 percent) experienced an improvement in overall liver histology, as measured by an improvement of at least two points in Knodell necroinflammatory score without worsening in Knodell fibrosis score.  Of the 94 patients who had cirrhosis (Ishak fibrosis score = 5) at the start of therapy, 69 (73 per cent) experienced regression of cirrhosis and 68 (72 per cent) had at least a two-point reduction in Ishak fibrosis score.

Among HBeAg-positive patients receiving Viread through 240 weeks (Study 103), the cumulative probability (estimated by Two-State Markov model) of “s” antigen loss and seroconversion was 9 per cent and 7 per cent, respectively. Additionally, no resistance to Viread emerged over 240 weeks of treatment.

According to Jenny Heathcote, medical director of the University of Toronto, Canada, and the principal investigator for Study 103.“Viral resistance is a significant challenge for physicians treating patients with chronic hepatitis B. These five-year results are important in that they demonstrate Viread’s high genetic barrier to resistance, which is essential for the long-term success of HBV therapy.”

Viread for HBV was approved by the US Food and Drug Administration (FDA) in 2008 and has since become the most-prescribed medicine for chronic HBV in the United States.  These five-year data have been submitted to the FDA and to the European Medicines Agency for review and potential inclusion in the Viread label.