October 31, 2000
Gilead Sciences Announces Preliminary Results from Study of Adefovir Dipivoxil 10 mg for the Treatment of Patients Co-infected with HIV and Chronic Hepatitis B
Data Presented at 51st AASLD Meeting
Dallas, Texas -- October 31, 2000
Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from an ongoing open-label pilot study evaluating the safety and efficacy of adefovir dipivoxil 10 mg once daily as a treatment for lamivudine-resistant chronic hepatitis B virus (HBV) infection in 35 patients co-infected with HIV and HBV. Preliminary results from this 12-month study show that treatment with adefovir dipivoxil 10 mg once daily is associated with a mean decrease in HBV DNA of 3.40 log10 copies/mL at 24 weeks. Gilead is currently conducting two placebo-controlled Phase III clinical trials to evaluate adefovir dipivoxil as a potential treatment for chronic HBV in non-HIV infected patients.
Preliminary data from this single-center study were presented at the 51st annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Dallas, Texas (Presentation #100671) by Dr. Yves Benhamou, Service d’Hépato-Gastroentérologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. Approximately 10 percent of HIV-infected patients also are carriers of HBV. Co-infection with HIV and HBV is associated with a higher prevalence of cirrhosis than is observed in patients who are HIV negative.
“Nearly 70 percent of patients with chronic HBV infection develop resistance after four years of treatment with lamivudine, and that number can be as high as 90 percent in patients who are co-infected with HIV and HBV,” commented Dr. Benhamou. “Given these statistics, it is encouraging that treatment with adefovir dipivoxil 10 mg appears to be well tolerated and results in a greater than 3 log10 reduction of HBV DNA at 24 weeks.”
Study Design and Results
This open-label study was designed to evaluate the safety and efficacy of adefovir dipivoxil 10 mg once daily for the treatment of lamivudine-resistant HBV infection in patients co-infected with HIV. The study enrolled 35 patients with controlled HIV infection (HIV RNA serum levels less than 2.60 log10 or 400 copies/mL). Patients had a mean HBV DNA serum level of 8.64 log10 copies/mL at baseline and documented lamivudine-associated resistance mutations in the YMDD domain of HBV polymerase, the viral enzyme targeted by both lamivudine and adefovir. Patients had received lamivudine 150 mg twice daily as part of their antiretroviral treatment regimen for a median of 42 months at study entry. HBV resistance to lamivudine was detected a median of 23.6 months prior to the initiation of treatment with adefovir dipivoxil 10 mg for chronic HBV infection.
In the preliminary analysis of this ongoing study, patients added adefovir dipivoxil 10 mg to their existing lamivudine therapy for a median treatment duration of 28 ± 5.7 weeks. HBV DNA levels were measured at baseline and monthly thereafter using a PCR assay. The mean decrease in HBV DNA from baseline was –3.40 log10 copies/mL (n=23) at week 24 (p<0.0001). At the time these data were analyzed, 10 patients had not yet reached the 24-week time point, and two patients had discontinued from study. One patient discontinued from study for reasons not related to treatment with adefovir dipivoxil; for the second patient, the role of adefovir dipivoxil in study discontinuation was not assessable. Based on analyses at each monthly time point, patients’ HBV DNA declined rapidly in response to treatment with adefovir dipivoxil. These data are consistent with in vitro studies demonstrating the potent activity of adefovir dipivoxil against both wild-type and lamivudine-resistant HBV. Adefovir dipivoxil was generally well tolerated, with no significant changes in serum ALT, serum electrolytes or renal function observed.
“We are pleased to see the demonstration of a rapid and potent antiviral response to treatment with adefovir dipivoxil 10 mg in Dr. Benhamou’s study. These data further support our development strategy for adefovir dipivoxil 10 mg,” said John C. Martin, Ph.D., President and Chief Executive Officer, Gilead Sciences.
Additional Resistance Data
Data further characterizing the resistance profile of adefovir dipivoxil also were presented today (Presentation #100750) at the AASLD conference. Genotypic and phenotypic analyses of HBV samples from 26 patients were conducted. These patients participated in two Phase II studies designed to evaluate the safety and efficacy of various doses of adefovir dipivoxil for the treatment of chronic HBV infection. Patients were treated with adefovir dipivoxil for up to 36 weeks, and no adefovir-associated resistance mutations were identified in the HBV polymerase gene in HBV samples isolated from these patients.
In addition to the presentations described above, additional in vitro, preclinical and clinical data from three studies characterizing the potential role of adefovir dipivoxil in the treatment of chronic HBV also were presented at AASLD.
Ongoing Adefovir Dipivoxil Phase III Program
Two pivotal Phase III trials are currently underway to evaluate adefovir dipivoxil monotherapy as a potential treatment for chronic HBV. Study 437, initiated in March 1999, is a randomized, double-blind, placebo-controlled trial of adefovir dipivoxil 10 and 30 mg being conducted in Australia, Europe, North America and Southeast Asia. Study 438, initiated in January 2000, is evaluating adefovir dipivoxil 10 mg for the treatment of patients with precore mutant HBV infection, a strain of the virus that has evolved without the hallmark HBV “e” antigen. This trial is being conducted in Australia, Canada, France, Greece, Israel, Italy and Southeast Asia. Both Phase III clinical trials are fully enrolled, and Gilead anticipates the presentation of data from the one year endpoint of these studies at scientific conferences during the second half of 2001.
In addition to these Phase III studies, Gilead also is conducting an open-label clinical trial, Study 435, designed to evaluate the use of adefovir dipivoxil for the treatment of lamivudine-resistant HBV in liver transplant recipients or pre-transplant patients. This study is being conducted in North America, Asia, Australia and Europe.
Glaxo Wellcome plc (NYSE: GLX), in collaboration with Gilead Sciences, initiated a controlled clinical trial in March 2000 designed to evaluate the once-daily use of adefovir dipivoxil 10 mg as combination therapy with lamivudine 100 mg (Epivir-HBV) in chronic HBV patients who have experienced diminished therapeutic response to lamivudine monotherapy. This 52-week randomized, double-blind, placebo-controlled trial will enroll 130 adult patients with chronic compensated or decompensated liver disease due to HBV infection and evidence of diminished therapeutic response to lamivudine. This study is being conducted in the United States, Australia, Canada, France, Hong Kong, Singapore, Spain and the United Kingdom.
Patients and physicians who would like more information about adefovir dipivoxil may contact Gilead Sciences Medical Information at 1-800-GILEAD-5 (1-800-445-3235) or 1-650-574-3000 from outside the United States.
Gilead Sciences, Inc., headquartered in Foster City, CA, is an independent biopharmaceutical company that seeks to provide accelerated solutions for patients and the people who care for them. Gilead discovers, develops, manufactures and commercializes proprietary therapeutics for challenging infectious diseases (viral, fungal and bacterial infections) and cancer. Gilead maintains research, development or manufacturing facilities in Foster City, CA; Boulder, CO; San Dimas, CA; Cambridge, UK and Dublin, Ireland and sales and marketing organizations 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 the safety, efficacy and resistance data observed in Gilead’s earlier clinical trials and preclinical testing may not be observed in Gilead’s more reliable Phase III clinical trials and risks related to regulatory approval of adefovir dipivoxil. 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, 1999 and in Gilead’s Quarterly Reports on Form 10-Q, all of which are on file with the U.S. Securities and Exchange Commission.
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