GILEAD ANNOUNCES INITIATION OF NIH-SPONSORED PHASE I TRIAL TO EVALUATE
TENOFOVIR TOPICAL GEL AS PREVENTIVE FOR VAGINAL TRANSMISSION OF HIV
(editorial note: you can read information, study results, and safety
information about Tenofovir at the NATAP website www.natap.org by using the
search engine for Tenofovir)|
Foster City, CA, May 21, 2002 - Gilead Sciences, Inc. (Nasdaq: GILD) today
announced the initiation of a collaborative Phase I clinical trial to
evaluate the safety and acceptability of the experimental topical gel
formulation of the antiviral tenofovir as a potential prevention method for
vaginal transmission of the human immunodeficiency virus (HIV). Tenofovir is
the active ingredient in Gileads oral antiretroviral drug Vireado (tenofovir
disoproxil fumarate), which was approved for marketing by the U.S. Food and
Drug Administration (FDA) in October 2001 and by the European Commission in
February 2002 as an anti- HIV treatment.
Phase I study (HPTN 050) is sponsored by the Division of AIDS of the National
Institute of Allergy and Infectious Diseases (NIAID), National Institutes of
Health (NIH), and is being conducted by the HIV Prevention Trials Network
under the auspices of Family Health International.
Recent statistics estimate that worldwide nearly 40 million adults and
children were living with HIV/AIDS at the end of 2000, and that each day
15,000 new HIV infections occur. Because the majority of HIV is transmitted
through heterosexual contact, public health experts have identified the need
for new ways to prevent the sexual transmission of HIV. While condom use has
been shown to prevent HIV transmission, public health experts point out that
women often are unable to negotiate the proper use of condoms by their male
"Tenofovir topical gel is a very exciting investigational microbicide because
it is the first one that contains an antiretroviral agent,ls said Lisa A.
Maslankowski, MD, Principal Investigator, University of Pennsylvania and
Co-Chair of the Phase I clinical trial. Unlike other microbicides, when HIV
comes in contact with an uninfected T-cell, tenofovir is already activated to
the HIV virus from replicating. If HIV is unable to reproduce, it is unlikely
to survive long enough to cause systemic infection.
"Even if the use of a topical microbicide, such as tenofovir, could prevent
half of the new HIV infections estimated to occur, that would potentially
mean that as many as 7,500 people each and every day could be spared from
contracting this terrible disease", continued Dr. Maslankowski.
Another compelling characteristic of tenofovir is its potent activity against
strains of HIV that have become resistant to other anti-HIV drugs,lV
explained Dr. Maslankowski. With the increasing incidence of patients who
become infected with multidrug-resistant HIV, it is important that a topical
microbicide remain active against a variety of HIV mutations. In vitro data
show that tenofovir is a potent inhibitor of many drug-resistant strains of
As a member of the novel class of antivirals called nucleotide analogues,
tenofovir is characterized by its ability to enter and inhibit viral repli
cation in infected and uninfected or resting cells, where it may form
protective reservoirs of active drug.
Tenofovir also has a long intracellular half-life, which is an important
characteristic for drugs designed to treat chronic viral infections.
About the Phase I Tenofovir Microbicide Study
This Phase I study (HPTN 050) will enroll up to 96 women and their male
sexual partners (as relevant) at three sites in Philadelphia, PA, New York,
NY and Providence, RI. During the study, tenofovir topical gel will be
applied intravaginally for 14 consecutive days with a 21-day follow-up
period. The dosage and frequency of treatment will be escalated to determine
optimal clinical dose. The antiviral efficacy of tenofovir topical gel will
not be evaluated in this Phase I study.
At the conclusion of the study, patients will be evaluated for signs of the
effects of daily use of tenofovir topical gel including symptoms of
irritation or other systemic side effects. Secondary endpoints include degree
of acceptance of the treatment by study participants and their sexual
partners. A subgroup of women will be tested to see if the active ingredient
in tenofovir gel is absorbed into the bloodstream.
This study protocol went through a rigorous peer-review process by NIH
committees and clinical researchers before being approved for conduct by the
HIV Prevention Trials Network, said Kenneth Mayer, MD, Principal
Investigator, Miriam Hospital and Brown University, Providence, RI and
Co-Chair of the Phase I clinical trial. The feedback we received indicates
that the research community is very enthusiastic about the potential
development of tenofovir as a topical microbicide.
Early Animal Data
Animal studies in monkeys have demonstrated the potential of tenofovir to
prevent transmission of simian immunodeficiency virus (SIV). Intravaginal
application of tenofovir gel, beginning 24 hours before and continuing for 48
hours after intravaginal inoculation with SIV, resulted in 100 percent
protection in four female rhesus macaques, compared with evidence of
infection in both of the two animals receiving placebo gel. In a separate
four-week study of macaques, daily subcutaneous injections of tenofovir,
beginning either 48 hours before or up to 24 hours after exposure to SIV,
resulted in 100 percent protection against acute SIV infection in 25 treated
animals. In comparison, all 10 animals receiving placebo 48 hours prior to
inoculation became infected. SIV infection in primates is a commonly used
evaluation model for HIV in humans.
We are pleased to be working with the NIAID to explore additional
applications of this important antiviral beyond the treatment setting. As a
topical microbicide gel, tenofovir may be able to help prevent the thousands
of new HIV infections that occur each year, and consequently help slow the
growing magnitude of the worldwide AIDS epidemic,ll said John C. Martin, PhD,
President and Chief Executive Officer of Gilead. iiFrom our controlled
clinical trials of the drug's oral formulation, Viread, we know that the
unique molecular properties of tenofovir can result in a valuable anti-HIV
treatment. We will continue to work with government, the advocacy community
and international health organizations to explore additional uses of
tenofovir to potentially extend its therapeutic benefits to a greater variety
of patient populations in need.
Tenofovir is the active ingredient in Gileads oral antiretroviral drug
Viread, which 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. The approved dose of Viread for the treatment of
infection is 300 mg once daily taken orally with a meal.
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
Viread 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
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.
Gilead Sciences, Inc.
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 five marketed products
and focuses its research and clinical programs on anti-infectives, including
antivirals, antifungals and antibacterials. Headquartered in Foster City, CA,
Gilead has operations in the United States, Europe and Australia.
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.
For example, in vitro and animal data for tenofovir referred to in this press
release cannot predict with certainty clinical success in humans.
Accordingly, there is a risk that these data will not be observed in human
studies. 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, 2001 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.
Note to Editors: The following are principal investigators in the tenofovir
gel microbicide study:
Wafaa El-Sadr, MD
New York, NY
Lisa Maslankowski, MD
University of Pennsylvania
Kenneth Mayer, MD
Miriam Hospital and