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Gilead Announces Preliminary Results from 48-Week Phase III Study of Emtricitabine in Patients with Chronic Hepatitis B
  FOSTER CITY, Calif.--(BUSINESS WIRE)--11/25/2003--Gilead Sciences, Inc. (Nasdaq:GILD) today announced preliminary results from a Phase III clinical trial (Study FTCB-301) comparing the efficacy and safety of emtricitabine 200 mg once daily versus placebo in patients with chronic hepatitis B. Preliminary results from this analysis demonstrate that treatment with emtricitabine 200 mg once daily for 48 weeks is associated with improvements in liver histology in 62 percent of patients who received the drug compared to 25 percent of patients who received placebo (p less than 0.001). Improvement in liver histology is an important marker of treatment benefit in patients with chronic hepatitis B, and the primary endpoint in this study. Gilead expects to present these data in detail at a scientific conference next year.
"Gilead is dedicated to the development and marketing of therapeutics to address the challenges in treating chronic hepatitis B, which remains under-diagnosed and significantly under-treated," said John C. Martin, PhD, President and CEO of Gilead Sciences. "With the data from the first large study of emtricitabine in hepatitis B now in hand, Gilead will continue to evaluate the development path for this compound moving forward."
Study Design
Study FTCB-301 is a 48-week, double-blind, placebo-controlled clinical trial conducted at 34 sites in seven countries in North America, Europe and Asia. The trial was designed to compare the efficacy and safety of emtricitabine 200 mg once daily versus placebo in 248 patients with chronic hepatitis B who had not previously received therapy with a nucleoside analogue. Patients were randomized (2:1) to receive emtricitabine 200 mg once daily or placebo for 48 weeks. Prior to study entry, all patients were hepatitis B surface ("s") antigen positive for at least six months. Both hepatitis B "e" antigen negative and hepatitis B "e" antigen positive patients were enrolled in the study. At study entry, patients were required to have elevated levels of the liver enzyme alanine aminotransferase (ALT) and detectable serum levels of HBV DNA.
Study Results
After 48 weeks, 62 percent of patients treated with emtricitabine 200 mg once daily exhibited significant improvements in liver histology, compared with 25 percent of patients receiving placebo (p less than 0.001). Improvement in liver histology is defined as a reduction from baseline of two points or more in the histological activity index (HAI) score and absence of progression in liver fibrosis using the Knodell scoring system.
Study FTCB-301 also examined changes after 48 weeks in HBV DNA (Digene Hybrid Capture II Assay), ALT levels, genotype mutations and serology. At baseline, emtricitabine and placebo patients had, respectively, median HBV DNA levels of 7.67 log10 copies/mL and 7.42 log10 copies/mL and median ALT of 81 IU/L and 92 IU/L. Treatment with emtricitabine resulted in a median reduction in HBV DNA from baseline of 3.00 log10 copies/mL compared with a median reduction in the placebo group of 0.44 log10 copies/mL (p less than 0.001). After 48 weeks, 56 percent of emtricitabine patients had HBV DNA below the assay lower limit of detection (4700 copies/mL) compared to seven percent in the placebo arm (p less than 0.001). Of the patients randomized to the emtricitabine arm of the study, 13 percent had virus with the YMDD mutation at week 48. The YMDD mutation in the HBV polymerase gene is known to confer resistance to emtricitabine and lamivudine. Additionally, patients treated with emtricitabine achieved a median ALT reduction of 52 IU/L, compared to a median ALT reduction of 25 IU/L for patients receiving placebo (p less than 0.001). In the subset of patients who were HBeAg-positive at baseline there was no significant difference between the treatment and placebo arms in the percentage of patients that achieved seroconversion, which is defined as both the disappearance of the hepatitis B "e" antigen (HBe-antigen negative) and the appearance of antibodies specific for this antigen (HBe-antibody positive).
Through 48 weeks, the discontinuation rate was similar between the treatment and placebo arms, with five percent of patients receiving emtricitabine and seven percent receiving placebo discontinuing from study. The most common adverse events were influenza, upper respiratory infection, headache, fatigue, abdominal pain, post-procedural pain (associated with liver biopsy) and cough. Additionally, there were no significant differences in the incidence of adverse events and grade 3 and 4 laboratory abnormalities between either arm of the study, with the exception of elevated ALT levels, which occurred more frequently in the placebo group.
Emtricitabine is a nucleoside analogue reverse transcriptase inhibitor. It works by blocking reverse transcriptase, an enzyme involved in the replication of HBV in the body. In addition to studies in patients with chronic hepatitis B, emtricitabine has been studied in patients with HIV. Approved in 2003, emtricitabine is marketed as Emtriva(TM) for use in combination with other antiretrovirals for the treatment of HIV infection in the United States and Europe.
In HIV clinical studies, more than 2000 HIV-infected adults have been treated with Emtriva for periods of 10 days to 200 weeks in Phase I, II and III clinical trials. Assessment of adverse events (without regard to relationship to study drug) is based on pooled data from two Phase III studies in which 571 treatment-naive and 440 treatment-experienced patients received Emtriva (n=580) or a comparator drug (n=431) for 48 weeks. The most common adverse events that occurred in patients receiving Emtriva were headache, diarrhea, nausea and rash, which were generally of mild to moderate severity. Approximately one percent of patients discontinued participation in the clinical studies due to these events. All adverse events were reported with similar frequency in Emtriva and control treatment groups with the exception of skin discoloration, which was reported with higher frequency in the Emtriva treated group. Skin discoloration, manifested by hyperpigmentation (excess pigmentation) on the palms and/or soles, was generally mild and asymptomatic. The mechanism and clinical significance of this adverse event are unknown. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals.
Chronic Hepatitis B
Hepatitis B is a serious disease that attacks the liver and can cause chronic (lifelong) infection, cirrhosis of the liver, liver cancer and death in up to a third of patients. Worldwide, there are approximately 400 million people with chronic hepatitis B, of which approximately one million people will die this year from complications from the disease, making chronic hepatitis B one of the 10 most common causes of death. Gilead currently markets Hepsera(R) (adefovir dipivoxil 10 mg) for the treatment of chronic HBV infection in both the United States and Europe. In April 2002, Gilead signed a licensing agreement with GlaxoSmithKline (GSK), granting GSK rights to commercialize Hepsera in Asia, Latin America and other territories.
About Gilead
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes therapeutics to advance the care of patients suffering from life-threatening diseases worldwide. The company has seven marketed products and focuses its research and clinical programs on anti-infectives. Headquartered in Foster City, CA, Gilead has operations in the United States, Europe and Australia.
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors that could cause actual results to differ materially from those referred to in the forward-looking statements. Such risks and uncertainties include the risk that these 48-week data will not be observed through longer treatment periods. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in the Gilead Annual Report on Form 10-K for the year ended December 31, 2002 and in Gilead's Quarterly Reports on Form 10-Q, all of which are on file with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead and Gilead assumes no obligation to update any such forward-looking statements.
Hepsera is a registered trademark and Emtriva is a trademark of Gilead Sciences, Inc.
For more information on Gilead Sciences, please visit the company's web site at www.gilead.com or call the Gilead Public Affairs Department at 1-800-GILEAD-5 or 1-650-574-3000.
CONTACT:Gilead Sciences, Inc. Susan Hubbard, 650-522-5715 (Investors) Erin Edgley, 650-522-5635 (Media)
SOURCE: Gilead Sciences, Inc.
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