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Gilead Announces Preliminary 48-Week Study Results Showing Viread Comparable to Stavudine in Treatment-Naive HIV Patients
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Foster City, CA, May 7, 2002 - Gilead Sciences, Inc. (Nasdaq: GILD) today announced preliminary data from a 48-week analysis of the company's ongoing Phase III clinical trial (Study 903) of Viread (tenofovir disoproxil fumarate). This study was designed to compare the efficacy and safety of a treatment regimen of Viread, lamivudine (3TC) and efavirenz to a regimen of stavudine (d4T), lamivudine and efavirenz in 600 antiretroviral-naive HIV patients. Preliminary results show that the Viread-containing regimen and the stavudine-containing regimen were both highly effective with comparable efficacy in HIV patients naive to therapy, as judged by the proportion of patients achieving suppression of HIV viral load at week 48. The U.S. Food & Drug Administration approved Viread for marketing in October 2001 and the European Commission granted approval in February 2002.
"This trial provides compelling evidence that Viread can be used as the cornerstone of a patient's first antiretroviral regimen," said John C. Martin, PhD, President and Chief Executive Officer of Gilead. "These data demonstrate that as a part of combination therapy for 48 weeks Viread can provide efficacy and safety comparable to stavudine, one of the most commonly prescribed nucleoside reverse transcriptase inhibitors."
Study Design
Study 903 is a three year, randomized, double-blind, active-controlled clinical trial conducted at 81 sites in the United States, Europe and South America. The trial was designed to compare the efficacy and safety of a treatment regimen of Viread, lamivudine (3TC) and efavirenz to a regimen of stavudine (d4T), lamivudine and efavirenz in 600 antiretroviral-naive patients with HIV infection. To maintain the blinded nature of the study, patients in the Viread arm received one tablet, twice daily of stavudine placebo while patients in the stavudine arm received one tablet, once daily of Viread placebo. Treatment assignments will remain blinded to patients and their physicians through 144 weeks.
The primary efficacy endpoint of the study is the proportion of patients in each arm achieving HIV RNA suppression below 400 copies/mL at week 48. Additional efficacy endpoints include the proportion of patients in each study arm who achieve viral suppression below 50 copies/mL at week 48, as well as increases in CD4 cell count. Data also were analyzed to determine 'responders', defined as the proportion of patients in each arm who achieved and maintained confirmed HIV RNA less than 400 copies/mL, and who have not discontinued from the study or added another antiretroviral drug through 48 weeks. Gilead anticipates submitting these 48-week interim data for presentation at a scientific conference later this year and to regulatory authorities for potential inclusion in the U.S. and European product labels.
Study Results:
At baseline, the mean HIV RNA for the intent-to-treat (ITT) population was 4.9 log10 copies/mL (about 100,000 copies/ml) and the mean CD4 cell count was 279 cells/mm3. The mean age of the study population was 36 years, 24 percent were female and 64 percent were Caucasian.
In the interim analysis of the ITT population, in which missing data are counted as failures, an identical 87 percent of patients in the Viread arm (n=299) and the stavudine arm (n=301) achieved suppression of HIV RNA below 400 copies/mL at 48 weeks of treatment (95% CI: -6%, +5%). When missing data are excluded (on treatment analysis), 95 percent of patients receiving Viread compared to 96 percent of patients receiving stavudine had reductions in HIV RNA to below 400 copies/mL (95% CI: -4%, +2%). Using the 'responder' analysis, 80 percent of patients receiving Viread compared to 82 percent of patients in the stavudine group had reductions in HIV RNA to below 400 copies/mL (95% CI: -9%, +3%).
The proportion of patients achieving HIV RNA suppression below 50 copies/mL was also evaluated in the study. The missing-equals-failure analysis demonstrates that 82 percent of patients in the Viread arm compared to 81 percent of patients in the stavudine arm achieved this result (95% CI: -6%, +6%). When missing data are excluded, 90 percent of patients in the Viread arm compared to 89 percent in the stavudine arm had reductions in HIV RNA to below 50 copies/mL (95% CI: -4%, +5%).
Additionally, patients in both treatment groups experienced significant increases in CD4 cell count. At 48 weeks, combination treatment including Viread was associated with a mean increase from baseline of 169 cells/mm3 and treatment including stavudine was associated with a mean increase from baseline of 167 cells/mm3.
In each treatment group, therapy was generally well tolerated and the study discontinuation rate was nine percent. The incidence of grade 3/4 adverse events in the Viread-containing study arm was 19 percent compared to 17 percent in the stavudine-containing study arm. The incidence of grade 3/4 laboratory abnormalities in the Viread arm was 28 percent compared to 31 percent in the stavudine arm.
About Viread
Viread is the first nucleotide analogue reverse transcriptase inhibitor (NtRTI) approved for the treatment of HIV in the United States and Europe. It was approved in the United States in October 2001 and was approved in the European Union in February 2002. The drug works by blocking reverse transcriptase, an enzyme involved in the replication of HIV. The approved dose of Viread for the treatment of HIV infection is 300 mg once daily taken orally with a meal.
In the United States, Viread is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection. This indication is based on analyses of plasma HIV-1 RNA levels and CD4 cell counts in a controlled study of Viread of 24 weeks duration and in a controlled, dose ranging study of Viread of 48 weeks duration. Both studies were conducted in treatment-experienced adults with evidence of HIV-1 viral replication despite ongoing antiretroviral therapy. Studies in antiretroviral-naive patients are ongoing; consequently, the risk-benefit ratio for this population has yet to be determined.
Viread is approved in Europe for use in combination with other antiretroviral agents for the treatment of HIV infection in patients who are experiencing early virological failure.
Safety Profile
Approximately 10,000 patients have been treated with Viread alone or in combination with other antiretroviral products for periods up to three years in clinical trials and expanded access programs. Assessment of adverse reactions is based on two studies (902 and 907) in which 653 treatment-experienced patients received treatment with Viread 300 mg (n=443) or placebo (n=210) for 24 weeks followed by extended treatment with the drug. Adverse event rates in the Viread group were similar to those in the placebo-treated patients.
The most common adverse events in patients receiving Viread were mild to moderate gastrointestinal events, such as nausea, diarrhea, vomiting and flatulence. Laboratory abnormalities observed in clinical studies occurred with similar frequency in the Viread and placebo-treated groups. 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.
About HIV/AIDS
More than 900,000 Americans and 560,000 Europeans are infected with HIV, the virus that causes acquired immunodeficiency syndrome (AIDS). Each year, approximately 560,000 U.S. and European patients receive anti-HIV treatment regimens. Treatment with antiretroviral agents is crucial to control viral load and delay the emergence of the debilitating AIDS-defining events.
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