U.S. Food and Drug Administration Approves Gilead's Letairis(TM) (ambrisentan) 5 mg and 10 mg Tablets for the Once-Daily Treatment of Pulmonary Arterial Hypertension (WHO Group 1) in Patients with WHO Functional Class II or III Symptoms



    Gilead Sciences, Inc. (Nasdaq:GILD) today announced that the U.S.
    Food and Drug Administration (FDA) has granted approval of
    Letairis(TM) (ambrisentan) 5 mg and 10 mg tablets. Letairis is an
    endothelin receptor antagonist (ERA) indicated for the once-daily
    treatment of pulmonary arterial hypertension (WHO Group 1) in patients
    with WHO Functional Class II or III symptoms to improve exercise
    capacity and delay clinical worsening. Letairis will be available in
    the United States early next week. Because of the risks of liver
    injury and birth defects, the product will be available through the
    Letairis Education and Access Program (LEAP), a restricted
    distribution program designed to help patients learn about the risks
    of Letairis.

    "PAH is a debilitating and life-threatening disease for which
    there remains a significant need for new treatments," said Lewis J.
    Rubin, MD, Professor of Medicine, University of California, San Diego.
    "The availability of new treatments such as ambrisentan is critical to
    our ability to help patients living with this serious disease."

    "All of us at Gilead extend our thanks to the investigators and
    patients who took part in the Letairis clinical trials, and we
    appreciate the hard work of the U.S. FDA to ensure this product
    reaches those in need as quickly as possible," said John C. Martin,
    PhD, President and CEO of Gilead Sciences. "As a company dedicated to
    advancing therapeutics for diseases that represent significant unmet
    medical needs, we look forward to partnering with the PAH community to
    help patients living with this disease."

    In two randomized, double-blind, 12-week, placebo-controlled Phase
    III clinical trials (ARIES-1 and ARIES-2) involving a total of 393
    patients, treatment with Letairis resulted in a significant
    improvement in six-minute walk distance. An increase in walk distance
    was observed after four weeks of treatment with each dose regimen of
    Letairis, with a dose-response observed after 12 weeks of treatment.
    In ARIES-1, placebo-adjusted mean and median changes from baseline of
    31 meters and 27 meters (p=0.008), respectively, were observed for the
    5 mg dose. Placebo-adjusted mean and median changes from baseline of
    51 meters and 39 meters (p less than 0.001), respectively, were
    observed for the 10 mg dose. In ARIES-2, placebo-adjusted mean and
    median changes from baseline of 59 meters and 45 meters (p less than
    0.001), respectively, were observed for the 5 mg dose.

    Treatment with Letairis also significantly delayed time to
    clinical worsening of PAH. Clinical worsening was defined as the first
    occurrence of death, lung transplantation, hospitalization for PAH,
    atrial septostomy, study withdrawal due to the addition of other PAH
    therapeutic agents, or study withdrawal due to early escape
    (progressive disease).

    The long-term follow-up of the patients who were treated with
    Letairis in the two pivotal studies and the open-label extension
    (n=383) shows that 95 percent were still alive at one year and 94
    percent were still receiving Letairis monotherapy. These uncontrolled
    observations do not allow comparison with a group not given Letairis
    and cannot be used to determine the long-term effect of Letairis.

    In ARIES-1 and ARIES-2, a total of 261 patients received Letairis
    at doses of 2.5, 5 or 10 mg once daily and 132 patients received
    placebo. The most common adverse events that occurred at a higher
    frequency among Letairis-treated patients compared to placebo in the
    ARIES-1 and ARIES-2 studies included (placebo-adjusted frequency):
    peripheral edema (6 percent), nasal congestion (4 percent), sinusitis
    (3 percent), flushing (3 percent) and palpitations (3 percent). Most
    adverse drug reactions were mild to moderate and only nasal congestion
    was dose-dependent.

    In addition to data from Phase III clinical trials, the Letairis
    approval is also supported by data from an uncontrolled, open-label
    study of 36 patients who had previously discontinued endothelin
    receptor antagonists (bosentan, an investigational drug, or both) due
    to aminotransferase elevations greater than three times the upper
    limit of normal(ULN). With a median follow-up period of 13 months and
    with 50 percent of patients increasing the dose of Letairis to 10 mg,
    no patients were discontinued for aminotransferase elevations. The
    most common adverse events observed were peripheral edema, headache,
    dyspnea and flushing. The study suggests that Letairis may be an
    option for patients who have experienced asymptomatic aminotransferase
    elevations on other ERAs after aminotransferase levels have returned
    to normal.

    "Just ten years ago, patients had few options available to combat
    their disease, but there is now an emerging sense of hope as awareness
    of this important disease grows and new treatments become available,"
    said Rino Aldrighetti, President and CEO of the Pulmonary Hypertension
    Association (PHA).

    About the Letairis Education and Access Program (LEAP)

    Because of the risks of liver injury and birth defects, Letairis
    is available only through a special restricted distribution program
    called the Letairis Education and Access Program (LEAP) by calling
    1-866-664-LEAP (1-866-664-5327). Only prescribers and pharmacies
    registered with LEAP are able to prescribe and distribute Letairis. In
    addition, Letairis may be dispensed only to patients who are enrolled
    in and meet all conditions of LEAP.

    About Gilead(TM)Solutions

    Gilead also today announced the launch of Gilead(TM)Solutions, a
    comprehensive set of programs designed to help patients navigate the
    reimbursement process for Letairis and help minimize barriers to
    treatment.

    "Gilead is committed first and foremost to patients," said Dr.
    Martin. "Our hope is that this program will ensure greater access to
    care for PAH patients with a variety of circumstances, including the
    often overlooked group of patients who have some form of prescription
    insurance but have prohibitively high out-of-pocket expenses."

    Gilead will assist most eligible privately-insured patients who
    have high monthly co-payments with a portion of their out-of-pocket
    expenses. Similarly, patients with Medicare prescription drug coverage
    or other government-funded insurance may receive assistance with
    co-payments and deductibles through two existing independent patient
    foundations. Some restrictions will apply. Gilead's reimbursement
    support team will guide patients to these resources and explain
    program eligibility guidelines and the amount of financial assistance
    available.

    Similar to programs Gilead has established for patients in other
    disease areas, including HIV/AIDS and chronic hepatitis B, uninsured
    or underinsured patients will have access to reimbursement counseling
    and support in applying for public insurance programs for which they
    may qualify.

    Gilead has also established a program that addresses the unique
    access issues that exist at the launch of a new product before
    formulary status and payer coverage levels are finalized. This will
    ensure that physicians and patients have immediate access to Letairis
    while Gilead's reimbursement support team works to identify
    appropriate financial assistance.

    Gilead Solutions programs and services will only be available
    following enrollment in LEAP.

    "Many PAH patients face significant financial barriers, such as
    prohibitively high co-payment expenses, while also struggling to
    navigate what can be a difficult treatment authorization process as
    well as a complicated reimbursement process, all while dealing with
    their PAH symptoms," said Joy Beckmann, RN, MSN, Chair, PH Resource
    Network, Pulmonary Hypertension Association and Senior Research
    Coordinator, Liu Center for Pulmonary Hypertension, Los Angeles
    Biomedical Research Institute at Harbor-UCLA Medical Center. "It's
    important that adequate programs are in place to ensure that patients
    are not denied access to treatment for financial reasons."

    WARNING: POTENTIAL LIVER INJURY

    Letairis can cause elevation of liver aminotransferases (ALT and
    AST) to at least three times the upper limit of normal (ULN). Letairis
    treatment was associated with aminotransferase elevations greater than
    three times ULN in 0.8 percent of patients in 12-week trials and 2.8
    percent of patients including long-term open-label trials out to one
    year. One case of aminotransferase elevations greater than three times
    ULN has been accompanied by bilirubin elevations greater than two
    times ULN. Because these changes are a marker for potentially serious
    liver injury, serum aminotransferase levels (and bilirubin if
    aminotransferase levels are elevated) must be measured prior to
    initiation of treatment and then monthly.

    Elevations in aminotransferases require close attention. Letairis
    should generally be avoided in patients with elevated
    aminotransferases greater than three times ULN at baseline because
    monitoring liver injury may be more difficult. If liver
    aminotransferase elevations are accompanied by clinical symptoms of
    liver injury (such as nausea, vomiting, fever, abdominal pain,
    jaundice, or unusual lethargy or fatigue) or increases in bilirubin
    greater than two times ULN, treatment should be stopped. There is no
    experience with the re-introduction of Letairis in these
    circumstances.

    CONTRAINDICATION: PREGNANCY

    Letairis is very likely to produce serious birth defects if used
    by pregnant women, as this effect has been seen consistently when it
    is administered to animals. Pregnancy must therefore be excluded
    before the initiation of treatment with Letairis and prevented
    thereafter by the use of at least two reliable methods of
    contraception unless the patient is unable to become pregnant. In
    women who can become pregnant, pregnancy tests should be obtained
    monthly.

    Important Safety Information

    The most common adverse events that occurred at a higher frequency
    among Letairis-treated patients compared to placebo included
    (placebo-adjusted frequency): peripheral edema (6 percent), nasal
    congestion (4 percent), sinusitis (3 percent), flushing (3 percent),
    palpitations (3 percent), nasal pharyngitis (2 percent), abdominal
    pain (2 percent), constipation (2 percent), dyspnea (1 percent) and
    headache (1 percent).

    Elevations of liver aminotransferases have been reported with
    Letairis and serious liver injury has been reported with related
    drugs. Patients should be monitored monthly for liver
    aminotransferases and treatment with Letairis should be discontinued
    if greater than five times the upper limit of normal or if signs or
    symptoms of liver dysfunction are observed.

    Letairis is not recommended in patients with moderate to severe
    hepatic impairment. For women of childbearing potential, Letairis
    treatment should only be initiated after a negative pregnancy test and
    only in those using at least two reliable methods of contraception.

    Decreases in hemoglobin concentration and hematocrit have followed
    administration of other endothelin receptor antagonists and were
    observed in clinical studies with Letairis. These decreases were
    observed within the first few weeks of treatment with Letairis, and
    stabilized thereafter.

    Peripheral edema is a known class effect of endothelin receptor
    antagonists and is also a clinical consequence of PAH and worsening
    PAH. In the placebo-controlled studies, there was an increased
    incidence of peripheral edema in patients treated with doses of 5 or
    10 mg of Letairis compared to placebo. Most edema was mild to moderate
    in severity. Peripheral edema was similar in younger patients (age
    less than 65 years) receiving Letairis (14 percent; 29/205) or placebo
    (13 percent; 13/104), and was greater in elderly patients (age greater
    than or equal to 65 years) receiving Letairis (29 percent; 16/56)
    compared to placebo (4 percent, 1/28). The results of such subgroup
    analyses must be interpreted cautiously.

    Caution should be used when Letairis is co-administered with
    cyclosporine A, as it may cause increased exposure to Letairis.

    Caution should be used when Letairis is co-administered with
    strong CYP3A-inhibitors (e.g., ketoconazole) or CYP2C19-inhibitors
    (e.g., omeprazole).

    No clinically relevant interactions of Letairis with warfarin or
    sildenafil have been observed.

    About Letairis(TM)

    Letairis(TM) (ambrisentan) is an endothelin receptor antagonist
    that is selective for the endothelin type-A (ET(A)) receptor.
    Activation of the ET(A) receptor by endothelin, a small peptide
    hormone, leads to vasoconstriction (narrowing of blood vessels) and
    cell proliferation. The clinical impact of high selectivity for ET(A)
    is not known. PAH is associated with elevated endothelin blood levels.

    GlaxoSmithKline holds rights to commercialize ambrisentan for PAH
    in territories outside of the United States. A Marketing Authorisation
    Application (MAA) for ambrisentan was filed with the European
    Medicines Agency (EMEA) earlier this year.

    About Pulmonary Arterial Hypertension

    PAH is a debilitating disease characterized by constriction of the
    blood vessels in the lungs leading to high pulmonary arterial
    pressures. These high pressures make it difficult for the heart to
    pump blood through the lungs to be oxygenated. Patients with PAH
    suffer from shortness of breath as the heart struggles to pump against
    these high pressures, causing such patients to ultimately die of heart
    failure. PAH can occur with no known underlying cause, or it can occur
    secondary to diseases such as connective tissue disease, congenital
    heart defects, cirrhosis of the liver and HIV infection. PAH afflicts
    approximately 200,000 patients worldwide.

    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. For more information on Gilead Sciences, please
    visit the company's website at www.gilead.com or call Gilead Public
    Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

    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 that Gilead(TM)Solutions will not provide greater access to care
    for PAH patients with a variety of circumstances. 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
    Annual Report on Form 10-K for the year ended December 31, 2006 and
    its Report on Form 10-Q for the first quarter of 2007, 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 Letairis is available at
    www.gilead.com and at www.Letairis.com.

    Letairis is a trademark of Gilead Sciences, Inc.

    For more information on Gilead Sciences, please visit the
    company's web site at www.gilead.com or call Gilead Public Affairs at
    1-800-GILEAD-5 or 1-650-574-3000.