To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: FDA Approves Ziagen For Inclusion In AIDS/HIV Combination Drug Therapy URL: http://www.pslgroup.com/dg/D532A.htm Doctor's Guide December 18, 1998
RESEARCH TRIANGLE PARK, NC -- Dec. 18, 1998 – The United States Food and Drug Administration has approved Glaxo Wellcome's Ziagen (abacavir sulfate) for use in combination with other drugs to treat HIV and AIDS. Ziagen is a new drug with proven antiviral activity, which is conveniently dosed with one pill twice daily and easily incorporated into multi-drug regimens. It is the first new drug in its class (nucleoside analogue reverse transcriptase inhibitors) to be approved in more than three years. Ziagen has been studied in clinical trials that have included previously untreated patients as well as heavily pre-treated patients -- including a large, well-controlled study in heavily pre-treated children. Studies show that combinations containing Ziagen have proven antiviral activity in patients who have not previously received treatment with antiretroviral drugs. Patients who have had prolonged prior exposure to Retrovir(R) (zidovudine; AZT) and Epivir(R) (lamivudine; 3TC) may have a minimal response to combinations containing Ziagen. However, studies have shown some of these patients to have experienced significant antiviral activity as a result of switching to new combinations containing Ziagen. Ziagen in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection. This indication is based on analyses of surrogate markers in controlled studies of up to 24 weeks in duration. At present, there are no results from controlled trials evaluating long-term suppression of HIV-RNA or disease progression with Ziagen. The approval of Ziagen is based on results from three phase III studies. In a planned interim analysis at 16 weeks of a study of adults with no previous treatment history, the three drug combination of Ziagen+Epivir+Retrovir was shown to be superior to the combination of Epivir+Retrovir in reducing HIV-1 RNA viral load. In this study, 75 percent of 87 patients on triple combination including Ziagen were at less than 400 copies/mL using the Roche Amplicor HIV Monitor(R)Test compared to 35 percent of 86 patients on dual therapy. Through 16 weeks of therapy, the median CD4 changes from baseline were 47 cells/mm3 in the group receiving Ziagen and 112 cells/mm3 in the placebo group. This difference was not statistically significant. In a planned interim analysis at 24 weeks of a study of children with extensive prior nucleoside treatment, the three drug combination of Ziagen+Epivir+Retrovir was shown to be superior to the combination of Epivir+Retrovir in reducing HIV-1 RNA viral load. In this study, 13 percent of 102 patients on triple combination including Ziagen were at less than 400 copies/mL using the Roche Amplicor HIV Monitor(R)Test compared to 2 percent of 103 patients on dual therapy. After 16 weeks of therapy, the median CD4 increases from baseline were 69 cells/mm3 in the group receiving Ziagen and 9 cells/mm3 in the control group. Preliminary findings from a second controlled study in therapy-naive adults were supportive of the efficacy of Ziagen through 16 weeks of treatment. This study compares Ziagen+Combivir(R) (lamivudine/zidovudine) with the combination of Crixivan(R) (indinavir; protease inhibitor)+Combivir, and is continuing through 48 weeks. "Ziagen appears to be a highly potent drug that will have potential in a variety of drug combinations because of its ease of dosing and the fact that it has a low likelihood of interactions with other antiretroviral drugs that are metabolised by the cytochrome P450 enzyme system," said Robert Schooley, M.D., professor of medicine at the University of Colorado Health Sciences Center. Ziagen will be dosed as one 300-mg tablet twice daily with no food or water restrictions or requirements. It is expected that Ziagen will be available in pharmacies in early January. In clinical trials to date, the most commonly reported adverse events were headache, nausea, vomiting, malaise and diarrhea when Ziagen was taken, primarily with Epivir and Retrovir but also with all marketed and most investigational compounds. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including abacavir and other antiretrovirals. The most serious adverse event associated with Ziagen is a hypersensitivity reaction that can be life threatening and has been fatal in some cases. The hypersensitivity reaction has been observed in approximately three to five percent of patients receiving Ziagen in clinical trials and is characterised by fever, skin rash, fatigue, and gastrointestinal symptoms, such as nausea, vomiting, diarrhea, or abdominal pain. The symptoms of this reaction get progressively worse if treatment continues. Patients experiencing these symptoms should stop taking Ziagen and contact a physician immediately. Symptoms of this reaction usually occur within the first six weeks of treatment and generally resolve following permanent discontinuation of Ziagen. Patients experiencing this reaction must not take Ziagen again as restarting the drug after a hypersensitivity reaction has resulted in cases of life-threatening and fatal reactions. --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. 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