In the longest-term Hepsera trial to date, Gilead Sciences Inc. reported that five-year treatment with its oral hepatitis B drug continues to demonstrate a regression in liver fibrosis.

Data presented at the 56th annual American Association for the Study of Liver Diseases meeting in San Francisco described the sustained safety and efficacy of Hepsera (adefovir dipivoxil) in patients with an antigen-negative, presumed precore mutant chronic form of hepatitis B.

Analysis of the first set of liver biopsies taken after five years of treatment show liver fibrosis regression in 75 percent of patients.

Liver fibrosis, characterized by the replacement of normal tissue with fibrous tissue and loss of functional liver cells, can result from the chronic liver inflammation caused by hepatitis.

The study, an open-label extension of one of the two registration trials that led to the FDA's approval of Hepsera in 2002 for chronic hepatitis B, provides evidence of long-term antiviral effect of the drug in a particularly hard-to-treat patient population, said Erin Edgley, spokeswoman for Foster City, Calif.-based Gilead.

"More importantly, the liver biopsies we've seen in year one, and then again in years two, four and five, are showing continual improvement in inflammation as well as regression of liver fibrosis, which are key data," she told BioWorld Today.

One of the biggest difficulties of long-term treatment in patients with HBeAG-negative hepatitis B is the development of genotypic resistance after only a few years.

The Hepsera trial is ongoing, Edgley said, and Gilead will "continue to do evaluations" in long-term safety and efficacy with the goal of ultimately expanding the product's label.

According to liver biopsies at the five-year (240-week) mark, 83 percent (20/24) and 75 percent (18/24) showed improvement in inflammation and regression of fibrosis, respectively. Sixty-nine percent (38/55) demonstrated improvement in liver function, as determined by normalization of serum alanine transferase levels. Of 55 patients, 37 - about 67 percent - exhibited suppression of viral replication, measured by levels of serum HVB DNA.

After five years of treatment, four patients experienced HBsAg loss, and three of those showed sAg seroconversion by the end of the evaluation.

The drug's safety profile has remained consistent. Overall, serious adverse events were reported in 19 percent (24/125) of patients in the study, though none were determined to be related to Hepsera. Four patients showed an increase in serum creatinine of 0.5 mg/dL or greater from baseline by week 240, and one of those patients discontinued treatment.

Hepsera is a nucleotide analogue that works against hepatitis B by inhibiting HBV DNA polymerase, an enzyme involved in the virus' replication. The drug is indicated for hepatitis B in adults with active viral replication, and for those with either signs of persistent elevations in serum aminotransferase or histologically active disease.

Gilead reported worldwide sales of Hepsera of $46.9 million for the third quarter.

The company has several other drugs in its pipeline for hepatitis, including an oral antiviral, tenofovir DF, in a Phase III program for chronic hepatitis B.

That program is testing tenofovir against Hepsera over a 48-week period. In August, Gilead and partner, New Haven, Conn.-based Achillion Pharmaceuticals Inc. began dosing patients in a Phase I study of GS 9132 for the treatment of hepatitis C.

Shares of Gilead (NASDAQ:GILD) fell 35 cents Tuesday to close at $51.64.

In other news from AASLD:

Human Genome Sciences Inc., of Rockville, Md., reported interim results from a Phase II trial showing that Albuferon (albumin-interferon alpha) in combination with ribavirin was well tolerated and demonstrated antiviral activity in patients with chronic hepatitis C who failed to respond to previous interferon alpha-based treatment regimens. To date, a total of 115 patients have been enrolled and randomized into five Albuferon treatment groups that are receiving subcutaneously administered doses of the drug, ranging from 900 mg to 1,800 mg, at intervals of either 14 or 28 days, in addition to daily oral RBV therapy. At week 24, 30 percent of the patients had no detectable hepatitis C RNA viral load, and antiviral activity was similar for the 14-day and 28-day Albuferon treatment cohorts. HGS has completed enrollment and initial dosing in a larger Phase IIb trial to test Albuferon in combination with ribavirin in patients with HCV genotype 1 who are na ve to interferon alpha-based treatment regimens.

Intarcia Therapeutics Inc., of Emeryville, Calif., said interim results from a Phase II study of omega interferon with or without ribavirin in interferon-na ve genotype 1 chronic HCV patients demonstrate that the combination of omega interferon and ribavirin is well tolerated and shows robust antiviral activity. Data indicated an early viral response rate of 84 percent. The study of daily subcutaneous omega interferon injections is intended to provide Intarcia with safety and clinical response data to support further development of the drug delivered by continuous release from the DUROS device. Omega DUROS is designed to deliver a consistent dose of omega interferon for three months after a single insertion in the upper arm.

Valeant Pharmaceuticals International Inc., of Costa Mesa, Calif., said interim 24-week data from a Phase II study of its oral antiviral compound, pradefovir mesylate, showed that the percentage of patients achieving undetectable HBV DNA (less than 400 c/mL) was significantly greater for patients receiving pradefovir, compared to those receiving Hepsera at doses of 10 mg, 20 mg, and 30 mg QD. In addition, those data show that the pradefovir 30 mg QD cohort achieved a 5.02 log¹⁰ drop in viral titers from baseline compared to a 3.66 log¹⁰ drop in the Hepsera group. Pradefovir is a prodrug of adefovir that was licensed from Metabasis Therapeutics Inc., of San Diego.