By Lisa Seachrist

Washington Editor

Gilead Sciences, Inc. has initiated the second pivotal trial in its Phase III program for adefovir dipivoxil as a therapy for chronic infections with the hepatitis B virus (HBV).

The trial, the second of two to be used to support regulatory filings, will focus on the precore mutant strain of HBV, which fails to produce the hallmark HBV "e" antigen. This strain of HBV may predispose patients to severe and progressive liver injury and has become the most prevalent form of HBV in many countries outside the U.S.

"We're doing this second pivotal study to create a more robust regulatory package," said Alison Murray, director of clinical research for Foster City, Calif.-based Gilead. "It's also going to give us data in a slightly different patient population, which will broaden our indication."

The study, referred to as Study 438, will evaluate 180 patients at 32 sites in Australia, Canada, France, Greece, Israel, Italy and Southeast Asia. It will be a randomized, double-blind, placebo-controlled trial testing 10 milligrams of adefovir dipivoxil daily vs. placebo in a two-to-one ratio for one year. At the end of the first year, patients receiving placebo will receive the drug. Patients who were on the active arm of the study will be further randomized to receive either drug or placebo again at a two-to-one ratio. The study endpoints are improvement in liver histology after one year of treatment and ability to suppress HBV DNA replication.

The first study, Study 437, was initiated in March 1999 and includes patients whose HBV infection produces the "e" antigen. That study will include 500 patients at 97 sites around the world. (See BioWorld Today, March 18, 1999, p. 1.)

Current treatments for hepatitis B include alpha interferon and lamivudine, a Glaxo Wellcome plc/BioChem Pharma Inc. drug from the same class as adefovir dipivoxil. However, many patients develop resistance to lamivudine after one year of treatment with the drug.

In early November, an FDA advisory panel refused to endorse higher doses of adefovir dipivoxil as a treatment for HIV infection. (See BioWorld Today, Nov. 2, 1999, p. 1.)

Gilead's stock (NASDAQ:GILD) closed at $67.406 a share, down $6.781, or 9 percent.