Gilead Announces New Letairis(R) (Ambrisentan) Data for the Treatment of Patients...

Gilead Announces New Letairis(R) (Ambrisentan) Data for the Treatment of Patients With Pulmonary Arterial Hypertension (WHO Group 1) With WHO Functional Class II or III Symptoms

-- Analysis of Ambrisentan Use in Patients Previously Receiving
Placebo in the ARIES-1 and ARIES-2 Studies Presented at the
International Conference of the American Thoracic Society --
TORONTO--(Business Wire)--
Gilead Sciences, Inc. (Nasdaq:GILD) today announced results of a
post-hoc analysis of data collected during the ARIES-1, ARIES-2 and
ARIES-E studies for Letairis(R) in pulmonary arterial hypertension
(PAH) (WHO Group 1) patients with primarily WHO functional class II or
III symptoms. This analysis compared one-year clinical outcomes for
PAH (WHO Group 1) patients who initially received placebo during the
12-week, placebo-controlled ARIES-1 and ARIES-2 studies before
receiving ambrisentan during a long-term, open-label extension study
(ARIES-E) to patients receiving continuous ambrisentan treatment
throughout the ARIES studies. Data from this analysis were presented
by Vallerie McLaughlin, MD, Associate Professor of Medicine, Director,
Pulmonary Hypertension Program at the University of Michigan Health
System, at ATS 2008 -- Toronto, the International Conference of the
American Thoracic Society, taking place May 16-21. Letairis
(ambrisentan 5 mg and 10 mg tablets) is indicated as a once-daily
treatment for PAH (WHO Group 1) in patients with WHO functional class
II or III symptoms to improve exercise capacity and delay clinical
worsening.

ARIES-1 and ARIES-2 were concurrent, double-blind,
placebo-controlled studies evaluating ambrisentan in PAH patients. The
studies primarily enrolled PAH patients with WHO functional class II
or III symptoms. These studies were identical in design except for the
investigative sites and doses of ambrisentan evaluated (ARIES-1: 5 or
10 mg; ARIES-2: 2.5 or 5 mg). In each study, patients were randomized
to receive placebo or ambrisentan orally once daily for 12 weeks. The
primary endpoint for each study was change in six-minute walk distance
(6MWD) from baseline to week 12. Following 12 weeks of treatment,
patients continued treatment with ambrisentan (ABS/ABS group, n=261)
or crossed over from treatment with placebo to ambrisentan (PLB/ABS
group, n=132) in ARIES-E.

In this analysis, one-year (48 weeks) clinical outcomes were
examined for patients in the ABS/ABS and the PLB/ABS groups.

Baseline for all patients was defined as the time of randomization
in ARIES-1 or ARIES-2. Clinical efficacy measures assessed in this
analysis included 6MWD and time to clinical worsening. Clinical
worsening was defined as the time from randomization to the first
occurrence of death, lung transplantation, hospitalization for PAH,
arterial septostomy, study withdrawal due to the addition of other PAH
therapeutics, or study withdrawal due to two or more early escape
criteria. A Kaplan-Meier analysis was used to evaluate time to
clinical worsening and includes all patients from the time of
randomization.

Study Results

Baseline characteristics were comparable between the ABS/ABS and
PLB/ABS groups. As previously reported, the change from baseline 6MWD
at week 12 in the ambrisentan group was +42 meters (95 percent CI: 34
to 51) compared to +3 meters in the placebo group (95 percent CI: -10
to 16). At week 12 of treatment, 96 percent of patients in the
ambrisentan group (95 percent CI: 93 percent to 98 percent) were
event-free, compared to 86 percent of patients in the placebo group
(95 percent CI: 80 percent to 92 percent).

At week 48, 6MWD in the ABS/ABS group was +47 meters (95 percent
CI: 35 to 59) compared to 33 meters in the PLB/ABS group (95 percent
CI: 16 to 50). Following the addition of ambrisentan to the placebo
group after week 12, the rate of clinical worsening decreased for the
PLB/ABS group. At one year of treatment, the probability of no
clinical worsening was 84 percent in the ABS/ABS group (95 percent CI:
80 percent to 89 percent) compared to 76 percent in the PLB/ABS group
(95 percent CI: 68 percent to 83 percent).

"Despite the availability of multiple therapies, PAH is often not
diagnosed in a timely manner, largely because classic PAH symptoms
such as shortness of breath and chest pain can be attributed to more
common medical conditions," said Dr. McLaughlin. "This data analysis
suggests that delay of initiation of an effective therapy like
ambrisentan may result in a decreased long-term improvement in
exercise capacity and an increased risk of disease progression for
patients with PAH, highlighting the importance of early diagnosis and
treatment."

During the first 12 weeks of treatment, three (2.3 percent)
placebo patients had liver aminotransferases (ALT or AST) elevations
greater than three times the upper limit of normal (ULN) compared to
zero patients in the ambrisentan group. After one year of treatment, a
total of four (3.0 percent) PLB/ABS patients and four (1.5 percent)
ABS/ABS patients had aminotransferase abnormalities greater than three
times ULN. Peripheral edema and headache occurred in greater than or
equal to 10 percent of patients in both the ambrisentan and placebo
groups during the first 12 weeks. By week 48, the adverse events
occurring in greater than or equal to 10 percent of patients in both
the ABS/ABS and PLB/ABS groups were peripheral edema, headache,
dizziness, dyspnea exacerbated, upper respiratory tract infection and
arthralgia. In addition, cough, nasal congestion and palpitations
occurred in greater than or equal to 10 percent of patients in the
ABS/ABS group. Nausea was observed in greater than or equal to 10
percent of patients in the PLB/ABS group. Right ventricular failure
was observed in greater than or equal to 10 percent of patients at
week 12 in the placebo group and at week 48 in the PLB/ABS group.

Data from this analysis comparing the PLB/ABS and ABS/ABS groups
during open-label follow-up treatment at 48 weeks have not been
reviewed by the U.S. Food and Drug Administration.

Full prescribing information for Letairis is available at
www.gilead.com and at
www.letairis.com/downloads/LETAIRIS_prescribing_information.pdf.

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. Obtain
monthly pregnancy tests.

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.

Important Safety Information

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.

In addition, there have been post-marketing reports of fluid
retention in patients with pulmonary hypertension, occurring within
weeks after starting Letairis. Patients required intervention with a
diuretic, fluid management, or, in some cases, hospitalization for
decompensating heart failure. Because the post-marketing experience
was reported voluntarily from a population of uncertain size, it is
not possible to reliably estimate the relative frequency or establish
a causal relationship to Letairis drug exposure.

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).

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).

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

Letairis is not recommended in patients with moderate to severe
hepatic impairment.

About Letairis

Letairis (ambrisentan) is an endothelin receptor antagonist that
has a high affinity for the endothelin type-A (ETA) receptor.
Activation of the ETA receptor by endothelin-1 (ET-1), a small peptide
hormone, leads to vasoconstriction (narrowing of blood vessels) and
cell proliferation. The clinical impact of high selectivity for ETA is
not known. Endothelin concentrations are higher in the lung tissue of
PAH patients, thus suggesting that ET-1 may play a critical role in
the pathogenesis or progression of PAH.

GlaxoSmithKline (GSK) holds rights to commercialize ambrisentan
for PAH in territories outside of the United States. On April 25,
2008, GSK announced that the European Commission issued a marketing
authorisation for ambrisentan, under the tradename Volibris(R), for
the treatment of PAH in patients classified as WHO functional class II
and III, to improve exercise capacity. GSK has stated that its first
European launches of Volibris are planned in the summer of 2008.

About Pulmonary Arterial Hypertension (WHO Group 1)

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.

Letairis is a registered trademark of Gilead Sciences, Inc.

Volibris is a registered trademark of Gilead Sciences, Inc.

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.

Gilead Sciences, Inc.
Patrick O'Brien, 650-522-1936 (Investors)
Nathan Kaiser, 650-522-1853 (Media)

Copyright Business Wire 2008