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Tenofovir 5 Year Efficacy/Safety Reported at Lipodystrophy Workshop
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Press announcement from Gilead
"LANDMARK FIVE-YEAR DATA ON GILEAD'S ANTI-HIV DRUG VIREAD
PRESENTED AT 8TH INTERNATIONAL WORKSHOP ON ADVERSE DRUG REACTIONS AND LIPODYSTROPHY"
-- Study Extension Will Provide Safety and Efficacy Data Out to Seven Years on Gilead's Leading Antiretroviral --
San Francisco, Calif., September 27, 2006 - Gilead Sciences, Inc. (Nasdaq: GILD) today announced two presentations of long-term efficacy and safety data from Study 903E on the company's leading oncedaily anti-HIV medication, Viread (tenofovir disoproxil fumarate). This clinical trial is an ongoing
open-label extension of Gilead's Study 903, a three-year double-blinded randomized clinical trial that compared once-daily Viread to twice-daily stavudine (d4T), both in combination with lamivudine and efavirenz in treatment-naive patients. A subset of patients who completed Study 903 were enrolled in
Study 903E and received two additional years of treatment with Viread, lamivudine and efavirenz. Long-term data were presented for patients who remained on a Viread-containing regimen for a total of five years and for those who switched from twice-daily stavudine to once-daily Viread upon enrollment in
Study 903E. Data from both analyses of Study 903E were presented this week at the 8th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, held September 24-26 in San Francisco (Posters #82 and #29).
"With the rapid progress in HIV therapy and the availability of potent, safe and well-tolerated regimens, long-term safety and efficacy data are increasingly important," said Norbert Bischofberger, PhD, Executive Vice President, Research and Development, Gilead Sciences. "Our decision to extend Study 903 four additional years to a total of seven years in duration underscores our commitment to helping physicians and patients properly assess the long-term impact of treatment on side effects such as lipodystrophy and changes in cholesterol."
Viread is a component of two once-daily fixed-dose combination tablets, Truvada (emtricitabine and tenofovir disoproxil fumarate), and ATRIPLA (efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg). ATRIPLA is the first and only once-daily single tablet regimen for the treatment of HIV-1 infection in adults as stand-alone therapy or in combination with other agents.
Study 903E
Study 903E is an ongoing four-year open-label extension for a subset of patients who successfully completed three years of treatment in Study 903. In Study 903, 600 patients were randomized and received treatment for three years with once-daily Viread (n=299) or twice-daily stavudine (n=301), both in combination with lamivudine and efavirenz. Patients who completed three years of treatment in Study 903 at sites in Argentina, Brazil and the Dominican Republic were rolled over into the open-label Study 903E extension.
Eighty-six patients randomized to receive three years of treatment in the once-daily Viread arm of Study 903 were rolled over into Study 903E and continued on the same regimen for two additional years. (Of these patients, nine discontinued prior to year five; four either withdrew consent, were non-compliant or lost to follow-up, two discontinued due to pregnancy, two experienced virologic failure and one discontinued due to an adverse event.) Eighty-five patients randomized to receive three years of treatment in the twice-daily stavudine arm of Study 903 were switched and received two additional years of open label therapy with a once-daily regimen of Viread, lamivudine and efavirenz in Study 903E. (Of these patients, two withdrew consent and discontinued prior to year five.)
Of the 86 patients from the Viread arm of Study 903 who entered 903E at year three, 83 percent experienced viral load suppression to less than 50 copies/mL following two additional years of treatment in Study 903E. These patients experienced a mean increase from baseline in CD4 count of 273 cells/mm3 at year three in Study 903. An additional mean increase in CD4 cell count of 148 cells/mm3 was observed from years three to five in Study 903E. No patient developed the K65R mutation during the open-label extension of the study.
Limb fat measurement was initiated in Study 903 at year two. Among Study 903E patients from the Viread arm of Study 903, mean total limb fat remained stable from years two to five (8.0 to 8.2 kilograms). There was no evidence of lipoatrophy among Viread-treated patients. Loss of limb fat, or peripheral lipoatrophy, is a hallmark of lipodystrophy, which has been associated with long-term administration of some anti-HIV medications and with HIV disease.
The overall adverse event profile observed during the open-label extension was similar to that seen in the first three years of the study. There were no discontinuations due to renal adverse events and no patient reported Fanconi syndrome. Additionally, there was no evidence of clinically relevant effects on bone mineral density related to Viread. One patient experienced bone fracture during the open-label extension phase which was trauma related and not associated with study drug.
In a second presentation, data were presented for patients randomized to the twice-daily stavudine arm of Study 903 who were switched and received two additional years of open-label therapy with once-daily Viread, lamivudine and efavirenz in Study 903E. Of the 85 patients from the stavudine arm of Study 903
who entered Study 903E at year three, 91 percent experienced viral load suppression to less than 50 copies/mL at two years in Study 903E. These patients experienced a mean increase from baseline in CD4 count of 343 cells/mm3 at year three in Study 903. An additional mean increase in CD4 cell count of 103 cells/mm3 was observed from years three to five in Study 903E. No patients discontinued treatment due to adverse events.
Study 903E patients in the twice-daily stavudine arm of Study 903 experienced a decrease in mean total limb fat from 5.0 kilograms at year two to 4.6 kilograms upon entering Study 903E. Following a switch to the once-daily Viread-containing regimen, an increase in mean total limb fat was observed (4.6 to 5.5 kilograms; p<0.001) at two years in Study 903E.
Study 903E patients in the twice-daily stavudine arm of Study 903 experienced a mean increase in fasting triglycerides of 102 mg/dL and mean increase in fasting total cholesterol of 59 mg/dL at year three in Study 903. Following a switch to the once-daily Viread-containing regimen, a mean decrease in fasting triglycerides of 75 mg/dL (p<0.001) and a mean decrease in fasting total cholesterol of 23 mg/dL (p<0.001) was observed at two years in Study 903E.
Among patients who switched from stavudine to Viread upon entry in Study 903E, no significant changes in bone mineral density (BMD) were observed at the spine and a mean decrease of 2.3 percent was observed at the hip (p<0.001) from years three to five in Study 903E. One patient experienced a fracture which was trauma related and not associated with study drug.
About Viread
In the United States, Viread is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Viread should not be used in combination with Truvada. Drug interactions have been observed when didanosine, atazanavir or lopinavir/ritonavir is coadministered with Viread and dose adjustments may be necessary. Data are not available to recommend a dose adjustment of didanosine for patients weighing less than 60 kg. Patients on atazanavir and lopinavir/ritonavir plus Viread should be monitored for Viread-associated adverse events, which may require discontinuation. When co-administered with Viread, it is recommended that atazanavir 300 mg be
given with ritonavir 100 mg. Atazanavir without ritonavir should not be co-administered with Viread.
Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported among patients taking Viread. Renal impairment occurred most often in patients with underlying systemic or renal disease or in patients taking concomitant nephrotoxic agents, though some cases have appeared in patients without identified risk factors.
Decreases in bone mineral density (BMD) at the lumbar spine and hip have been seen with the use of Viread. The effects of Viread-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown. Redistribution and/or accumulation of body fat have been
observed in patients receiving antiretroviral therapy. Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy including Viread.
The most common adverse events among patients receiving Viread with other antiretroviral agents in clinical trials were mild to moderate gastrointestinal events and dizziness. Moderate to severe adverse events occurring in more than 5 percent of patients receiving Viread included rash (rash, pruritis, maculopapular rash, urticaria, vesiculobullous rash and pustular rash), headache, pain, diarrhea,
depression, back pain, fever, nausea, abdominal pain, asthenia and anxiety (Study 903). Less than 1 percent of patients discontinued participation because of gastrointestinal events (Study 907).
The parent compound of Viread was discovered through a collaborative research effort between Dr. Antonin Holy, Institute for Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic (IOCB) in Prague and Dr. Erik DeClercq, Rega Institute for Medical Research, Katholic University in Leuven, Belgium.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Australia. Visit Gilead on the World Wide Web at www.gilead.com.
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. 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, 2005, filed 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.
Full prescribing information for Viread is available at www.viread.com.
Viread and Truvada are registered trademarks of Gilead Sciences, Inc.
ATRIPLA is a trademark of Bristol-Myers Squibb & Gilead Sciences, LLC.
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