By Kim Coghill

Washington Editor

Gilead Sciences Inc. is likely to file a new drug application during the first half of 2002 for its chronic hepatitis B product, adefovir dipivoxil.

The company may seek accelerated approval, meaning the 10-mg oral treatment that is expected to generate $300 million to $500 million annually for Gilead could be on the market late next year, Scott Stromatt, vice president and senior analyst for agriculture research and life sciences for C.E. Unterberg, Towbin in Denver, told BioWorld Today.

¿In Gilead¿s studies they are seeing seroconversion, and that¿s positive. If you can delay the development of cirrhosis, that¿s very significant, and they aren¿t seeing the scarring in the liver. They are seeing improvement,¿ Stromatt said.

Stromatt is speaking of Gilead¿s release Wednesday of preliminary data from a Phase III clinical study of adefovir dipivoxil in patients with precore mutant chronic hepatitis B virus (HBV). Precore is a strain that has mutated, preventing the virus from producing the ¿e¿ antigen, a protein the virus produces that makes it recognizable to the host (human) immune system.

¿Because precore mutant HBV doesn¿t produce e-antigen, it is much easier for the virus to go undetected and therefore preventing the body from launching an immune attack,¿ Sheryl Meredith, director of corporate communications for Foster City-Calif.-based Gilead, told BioWorld Today.

The data are from Study 438, an international, multicenter, double-blind, placebo-controlled trial of 185 patients in Australia, Canada, France, Greece, Israel, Italy and Southeast Asia.

Earlier this summer, Gilead released data from a 515-patient trial (Study 437) indicating that adefovir dipivoxil in naove chronic hepatitis B patients showed no resistance mutations. (See BioWorld Today, June 25, 2001.)

Adefovir dipivoxil is an antiviral reverse transcriptase inhibitor. Several years ago Gilead was developing and studying the drug for HIV patients but abandoned the plan after an FDA advisory panel failed to endorse the product for that indication. (See BioWorld Today, Nov. 3, 1999.)

When Gilead files for regulatory approval in the first half of next year, Meredith said the FDA will determine whether the new drug application (NDA) will be reviewed under an accelerated timeline.

But as Stromatt said, fast approval is necessary because there¿s nothing else on the market, except 3TC (lamivudine), for this indication. The problem with 3TC, he said, is that people develop a resistance to it and there are about 300 million to 350 million people worldwide who are affected by HBV.

In the developed world (U.S., European Union and Japan) Stromatt said there are about 3.5 million people who are chronically infected and about 1 million of them should be on therapy. ¿The market is about as big as the HIV market,¿ he said.

Study 438 demonstrated treatment with adefovir dipivoxil 10 mg once daily for 48 weeks is associated with improvements in liver histology in 64 percent of patients who received the drug compared to 33 percent of patients who received placebo (p=0.0002). Change in liver histology is an important marker of disease progression in patients with chronic HBV infection and the primary endpoint of the study, a statement from the company said.

¿The study continues to confirm the significant anti-HBV activity of the compound and also confirms its very positive safety profile, further demonstrating its utility as a potential long-term treatment for chronic hepatitis B,¿ Meredith said. ¿In addition, the study also continued to show that the compound has a very favorable resistance profile.¿

On Oct. 3, Gilead is scheduled to go before the FDA¿s Antiviral Drugs Advisory Committee for a hearing on its new drug application for Viread (tenofovir disoproxil fumarate) tablets, an HIV treatment.

Gilead¿s stock (NASDAQ:GILD) gained $1.20 Wednesday to close at $50.25.