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Phase IV Program Initiated for Ambrisentan

FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq:GILD - News) today announced the initiation of ATHENA-1, a Phase IV, randomized, double-blind, placebo-controlled study evaluating Letairis® (ambrisentan 5 mg and 10 mg tablets) in patients with pulmonary arterial hypertension (PAH) demonstrating a sub-optimal response to sildenafil monotherapy. ATHENA-1 is the first of several Phase IV Letairis studies Gilead plans to initiate in 2008 and 2009. Letairis is currently approved 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.

“The PAH research community has made great progress over the last several decades in developing therapies for patients, including establishing an understanding of the role of therapies targeting different disease pathways,” said Norbert Bischofberger, Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. “With our Phase IV program, we hope to contribute to the growing body of knowledge about this disease.”

About ATHENA-1
ATHENA-1 will evaluate whether the addition of Letairis to sildenafil is safe and effective in PAH patients who have not demonstrated an optimal response on sildenafil therapy alone. The primary objective of this study is to compare the change in pulmonary vascular resistance (PVR), or the resistance to blood flow caused by constricted lung blood vessels. A progressive increase in PVR is a measurable biological characteristic of PAH.

A total of 80 patients (40 in each arm) will be randomized to receive either Letairis or placebo, in addition to sildenafil at their current dose. The primary endpoint is the change from baseline in PVR after 24 weeks of treatment. Long-term safety and efficacy measures will be examined for up to one year (48 weeks).

Additional information regarding ATHENA-1 can be found at https://clinicaltrials.gov/.

Letairis is not indicated for use in combination with sildenafil for treatment of PAH.

Full prescribing information for Letairis is available at www.gilead.com and at https://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: Pregenancy
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 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.

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.

Source: Gilead Sciences

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