GILEAD INITIATES STUDY 934, A 48-WEEK CLINICAL TRIAL EVALUATING VIREAD
AND EMTRIVA VERSUS COMBIVIR
Press Release from Gilead Sciences
Foster City, CA, August 11, 2003 - Gilead Sciences (Nasdaq: GILD) today
announced that the company has initiated enrollment in Study 934. This Phase III
study is designed to assess the efficacy of a once-daily regimen containing
Viread® (tenofovir disoproxil fumarate) and Emtriva™ (emtricitabine) in
combination with efavirenz versus a regimen containing Combivir® (lamivudine 150
mg/zidovudine 300 mg), which is dosed twice daily, and efavirenz.
"We are pleased that this important study is underway, particularly because
there is increasing demand in the medical community for once-daily regimens for
HIV," said John C. Martin, PhD, President and CEO of Gilead Sciences. "We
believe that data obtained from this clinical trial will help physicians design
the best regimens for their patients."
Study 934 is an open-label, multicenter clinical trial that will enroll 300
HIV-infected patients in the United States and Europe. Participants in one arm
of the study will receive Viread 300 mg, Emtriva 200 mg and efavirenz 600 mg,
all dosed once daily. Patients in the comparator arm will receive Combivir
(lamivudine 150 mg/zidovudine 300 mg) twice daily and efavirenz 600 mg once
daily. All participants will be treatment-naive, meaning they will not
previously have received antiretroviral therapy.
The Centers for Disease Control and Prevention (CDC) estimate that 950,000
Americans are infected with HIV, the virus that causes acquired immunodeficiency
syndrome (AIDS). Approximately 360,000 infected individuals are receiving
antiretroviral treatment for HIV infection in the United States today.
In the United States, Viread is indicated 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 the first nucleotide analogue reverse transcriptase inhibitor
(NtRTI) approved for the treatment of HIV in the United States and Europe. The
drug works by blocking reverse transcriptase, an enzyme involved in the
replication of HIV. Viread is dosed as one tablet once daily taken orally with a meal.
In clinical trials and expanded access programs, approximately 10,000
patients have been treated with Viread alone or in combination with other
antiretroviral products for periods up to four years. To date, an estimated 150,000
patients have been prescribed Viread as part of their combination regimen.
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 these patients 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.
In clinical practice, a number of adverse events, including renal impairment,
nausea, rash and asthenia (weakness) have been reported. Renal impairment
occurred most often in patients with underlying systemic or renal disease, or in
patients taking concomitant nephrotoxic agents. 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
In the United States, Emtriva is indicated in combination with other
antiretroviral agents for the treatment of HIV-1 infection in adults. This indication
is based on the analyses of plasma HIV RNA levels and CD4 cell counts in two
Phase III clinical trials of Emtriva of 48 weeks duration in
antiretroviral-naive patients and antiretroviral treatment-experienced patients who were
virologically suppressed on an HIV treatment regimen. In antiretroviral
treatment-experienced patients, the use of Emtriva may be considered for adults with HIV
strains that are expected to be susceptible to Emtriva as assessed by
genotypic or phenotypic testing.
The drug is a nucleoside analogue reverse transcriptase inhibitor (NRTI) that
works by blocking reverse transcriptase, an enzyme involved in the
replication of HIV. Emtriva is dosed as one capsule once daily taken orally with or
without food. More than 2000 HIV-infected adults have been treated with Emtriva
for periods of 10 days to 200 weeks in Phase I, II and III clinical trials.
Assessment of adverse events is based on pooled data from two Phase III
studies in which 571 treatment-naive and 440 treatment-experienced patients
received Emtriva (n=580) or a comparator drug (n=431) for 48 weeks. The most common
adverse events that occurred in patients receiving Emtriva were headache,
diarrhea, nausea and rash, which were generally of mild to moderate severity.
Approximately one percent of patients discontinued participation in the clinical
studies due to these events. All adverse events were reported with similar
frequency in Emtriva and control treatment groups with the exception of skin
discoloration, which was reported with higher frequency in the group treated with
Emtriva. Skin discoloration, manifested by hyperpigmentation (excess
pigmentation) on the palms and/or soles, was generally mild and asymptomatic. The
mechanism and clinical significance of this adverse event are unknown.
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. In chronic hepatitis B infected patients
exacerbations of hepatitis B have been reported after discontinuation of Emtriva,
and patients co-infected with HIV and HBV should be closely monitored after
stopping Emtriva treatment. Patients with renal impairment should be carefully
monitored and may require dose interval adjustments.
An application for marketing approval of Emtriva for the treatment of HIV was
submitted to the European regulatory authorities in December 2002. On July
24, 2003, the European Union's Committee for Proprietary Medicinal Products
(CPMP), the scientific committee of the European Medicines Evaluation Agency
(EMEA), recommended granting Marketing Authorisation for Emtriva in the 15 member
states of the European Union.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and
commercializes therapeutics to advance the care of patients suffering from
life-threatening diseases worldwide. The company has seven marketed products and
focuses its research and clinical programs on anti-infectives. Headquartered in
Foster City, CA, Gilead has operations in the United States, Europe and
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, including the risk related to the
stability, pharmacokinetics and ultimately the company's ability to obtain regulatory
approval of a co-formulation of Emtriva and Viread and the risk that the EMEA
may not follow the recommendation of the CPMP and grant regulatory approval
of Emtriva in the European Union. These risks, uncertainties and other factors
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, 2002 and in
Gilead's Quarterly Reports on Form 10-Q, all of which are on file 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.