– First Agent Indicated for Uninfected Adults at High Risk of
Acquiring HIV Through Sex –
Gilead Sciences, Inc. (Nasdaq:GILD) today announced that the U.S. Food
and Drug Administration (FDA) has approved once-daily oral Truvada®
(emtricitabine and tenofovir disoproxil fumarate), in combination with
safer sex practices, to reduce the risk of sexually acquired HIV-1
infection in adults at high risk. Truvada is the first agent to be
approved for HIV prevention in uninfected adults, a strategy called
pre-exposure prophylaxis (PrEP). As part of the approval, Gilead worked
with the FDA to develop a Risk Evaluation and Mitigation Strategy (REMS)
to help ensure safe use of Truvada for PrEP as part of a comprehensive
prevention strategy. Truvada was originally approved in 2004 in
combination with other antiretroviral agents as a treatment of HIV-1
infection in adults and is currently the most-prescribed antiretroviral
product in the United States.
“Today’s decision is the culmination of almost 20 years of research
involving investigators, academic and medical institutions, funding
agencies and nearly 20,000 trial participants around the world, and
Gilead is proud to have been a partner in this effort,” said Norbert
Bischofberger, PhD, Executive Vice President, Research and Development
and Chief Scientific Officer, Gilead Sciences. “This advancement in the
field of HIV prevention was made possible due to the leadership and
commitment of the FDA and the Department of Health and Human Services to
reduce the number of new HIV infections in the United States and
worldwide.”
It is estimated that 1.2 million Americans are currently living with
HIV, and, despite the availability of existing prevention tools such as
condoms, the incidence rate has remained steady over the past two
decades with approximately 50,000 new infections occurring each year.
Nearly one-quarter (23 percent) of new HIV cases occur among women, and
more than half (61 percent) occur among men who have sex with men (MSM).
In particular, young African American MSM bear a heavy burden of the
epidemic, with new HIV cases among this group increasing by nearly 50
percent between 2006 and 2009.
Data supporting the approval of Truvada for PrEP came primarily from two
large placebo-controlled trials known as the Pre-Exposure Prophylaxis
Initiative (iPrEx), sponsored by the U.S. National Institutes of Health
(NIH) and the Bill and Melinda Gates Foundation, and Partners PrEP,
sponsored by the University of Washington and funded by the Bill and
Melinda Gates Foundation. The iPrEx and Partners PrEP trials found that
Truvada reduced the risk of acquiring HIV infection by 42 percent and 75
percent, respectively. Several other clinical studies also support the
use of Truvada for HIV risk reduction.
“This approval is a major milestone in our 30-year fight against AIDS,”
said Robert M. Grant, MD, MPH, Betty Jean and Hiro Ogawa Endowed
Investigator, Gladstone Institute of Virology and Immunology, University
of California, San Francisco and lead investigator of the iPrEx trial.
“The use of PrEP alongside routine HIV testing gives us a tremendous
opportunity to reduce the rate of new HIV infections in this country and
around the world.”
Based on the iPrEx results, in January 2011 the Centers for Disease
Control and Prevention (CDC) issued interim guidance on Truvada as PrEP
among high-risk adult MSM. CDC is currently developing formal U.S.
Public Health Service guidelines for the use of PrEP among both men and
women, which will address procedures for HIV testing and health
screening prior to PrEP initiation, as well as ongoing monitoring for
cases of HIV infection that may occur despite PrEP use, possible drug
resistance among those who become infected, side effects and clinical
toxicities.
“The data clearly demonstrate that Truvada as pre-exposure prophylaxis
is effective at reducing the risk of HIV infection acquired through
sexual exposure,” said Connie Celum, MD, MPH, Professor of Global Health
and Medicine at the University of Washington and lead investigator of
the Partners PrEP trial. “It is exciting to consider the potential
impact of this new HIV prevention tool, which could contribute to
significantly reducing new HIV infections as part of a combination HIV
prevention strategy. Although the implementation of PrEP will bring
challenges, they can be anticipated and systems developed to address
these challenges. In particular, systems to provide comprehensive
education and support to health care providers and people who use PrEP
will be required to ensure appropriate and effective use of this
potentially groundbreaking new HIV prevention intervention.”
As part of the REMS developed by Gilead and FDA to ensure safe use of
Truvada for PrEP, Gilead has developed FDA-approved materials to educate
and inform healthcare providers and uninfected individuals about Truvada
for PrEP. These materials highlight the importance of strict adherence
to the dosing regimen, emphasize that Truvada must be considered as only
one part of a comprehensive prevention strategy to reduce the risk of
HIV-1 infection and convey that Truvada for PrEP should only be used in
individuals who are confirmed HIV negative and HIV-1 screening should be
repeated at least every three months while taking Truvada for PrEP.
Truvada for PrEP should not be initiated when clinical signs or symptoms
consistent with acute HIV-1 infection are present.
As a separate measure to support the safe use of Truvada for PrEP,
Gilead also will provide vouchers for free HIV testing and condoms, an
opt-in service for regular reminders about HIV testing and subsidized
HIV resistance testing for any individual who becomes HIV-positive while
taking Truvada for PrEP.
In all studies of Truvada for PrEP, the most commonly reported side
effects included headache, stomach discomfort and weight loss. The
incidence and types of side effects were consistent with Truvada’s
safety and tolerability profile when used as an HIV treatment, which is
supported by more than four million years of patient use. Overall, there
have been nearly nine million patient years of experience with
tenofovir-containing regimens.
Important Safety Information about Truvada:
WARNINGS: Lactic acidosis and severe hepatomegaly with steatosis,
including fatal cases, have been reported with the use of nucleoside
analogs, including Viread®, a component of
Truvada, in combination with other antiretrovirals.
Truvada is not approved for the treatment of chronic hepatitis B
virus (HBV) infection and the safety and efficacy of Truvada have not
been established in patients coinfected with HBV and HIV-1. Severe acute
exacerbations of hepatitis B have been reported in patients who are
coinfected with HBV and HIV-1 and have discontinued Truvada. Hepatic
function should be monitored closely with both clinical and laboratory
follow-up for at least several months in patients who are coinfected
with HIV-1 and HBV and discontinue Truvada. If appropriate, initiation
of anti-hepatitis B therapy may be warranted.
Truvada used for a PrEP indication must only be prescribed to
individuals confirmed to be HIV-negative immediately prior to initiating
and periodically during use. Drug-resistant HIV-1 variants have
been identified with use for Truvada for a PrEP indication following
undetected acute HIV-1 infection. Do not initiate Truvada for a
PrEP indication if signs and symptoms of acute HIV infection are present
unless a negative infection status is confirmed.
Do not use Truvada for pre-exposure prophylaxis in individuals with
unknown or positive HIV status. Truvada should be used in
HIV-infected patients only in combination with other antiretroviral
agents.
New onset or worsening of renal impairment may occur, including
acute renal failure and Fanconi Syndrome. Creatinine clearance should be
calculated prior to administering Truvada. Truvada for HIV-1 infection
should not be used in patients with severe renal disease (CrCl < 30
mL/min), and routine monitoring of CrCl and serum phosphorous all
patients at risk for renal impairment is recommended. Avoid
administering concurrently with or with recent use of nephrotoxic drugs.
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Do not use Truvada for pre-exposure prophylaxis in individuals
with a creatinine clearance (CrCl) below 60 mL/min. Re-assess risk and
benefits of using Truvada for PrEP if a decrease in CrCL is observed
during use for PrEP.
Decreases in Bone Mineral Density (BMD) may occur. Consider
assessing BMD in individuals with a history of pathologic fracture or
other risk factors for osteoporosis or bone loss. Fat Redistribution has
also been observed in patients receiving antiretroviral therapy. Immune
Reconstitution Syndrome may occur in HIV-1-infected patients.
Autoimmune disorder may occur in the setting of Immune Reconstitution.
Truvada for a PrEP indication:
Comprehensive Management to Reduce the Risk of Acquiring HIV: Truvada
for PrEP should only be used as part of a comprehensive prevention
strategy that includes other prevention measures such as safer sex
practices. A comprehensive prevention strategy includes consistent and
correct use of condoms, the individual knowing both their and their
partner’s HIV status, getting regular testing for HIV and other sexually
transmitted infections, and informing individuals about and supporting
their efforts to reduce sexual risk behavior.
Use Truvada for PrEP to reduce the risk of acquiring HIV-1 only in
individuals confirmed to be HIV negative because HIV-1 resistance
substitutions may emerge. HIV-1 negative status must be confirmed
immediately prior to prescribing and regularly thereafter (at least
every three months). Defer initiating Truvada for PrEP if clinical signs
and symptoms of acute HIV-1 infection are present or if recent exposure
(< 1 month) is suspected, or confirm HIV-1 negative status using a test
approved by the FDA to aid diagnosis of acute or primary HIV-1
infection. While individuals are on TRUVADA for PrEP, discontinue if
symptoms of acute infection develop after a potential HIV-1 exposure
event until negative HIV-1 status can be confirmed using a test approved
by the FDA to aid in the diagnosis of acute or primary HIV-1 infection.
Truvada for use with other antiretroviral agents to treat HIV-1
infection: Truvada should not be co-administered with any other
antiretroviral agents for HIV that contain emtricitabine or tenofovir
disoproxil fumarate, nor should it be co-administered with products
containing lamivudine. Do not administer with Hepsera.
Common side effects reported during clinical studies with Truvada (in
combination with efavirenz) include diarrhea, nausea, fatigue, headache,
dizziness, depression, insomnia, abnormal dreams and rash.
In clinical trials for Truvada for PrEP, the most common side effects
associated with Truvada were headache, stomach discomfort and weight
loss. Caution should be exercised when co-administering Truvada with
didanosine, atazanavir and lopinavir/ritonavir due to the potential for
toxicity.
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 Asia
Pacific.
Forward-Looking Statement
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
risks that physicians and patients may be reluctant to use Truvada for
HIV risk reduction. As a result, there may not be significant use of
Truvada as a risk reduction tool. 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 Gilead’s Quarterly Report on Form 10-Q for
the quarter ended March 31, 2012, as 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.
U.S. full prescribing information for Truvada is available at www.Truvada.com.
Truvada is a registered trademark of Gilead Sciences, Inc.
For more information on Gilead Sciences, please visit the company’s
website at www.gilead.com,
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or call Gilead Public Affairs at 1-800-GILEAD-5
or
1-650-574-3000.
