Gilead Sciences, Inc. (Nasdaq: GILD) today announced two
presentations of long-term efficacy and safety data from Study 903E on
the company's leading once-daily anti-HIV medication, Viread(R)
(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(R) (emtricitabine and tenofovir disoproxil fumarate),
and ATRIPLA(TM) (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/mm(3) at year three in Study 903. An
additional mean increase in CD4 cell count of 148 cells/mm(3) 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/mm(3) at year
three in Study 903. An additional mean increase in CD4 cell count of
103 cells/mm(3) 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 less than 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 less
than 0.001) and a mean decrease in fasting total cholesterol of 23
mg/dL (p less than 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 less than 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.
