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FDA Approves New Treatment Combination of Gilead’s Letairis with Tadalafil for Pulmonary Arterial Hypertension (WHO Group 1)

FOSTER CITY, Calif.--(BUSINESS WIRE)--Oct. 2, 2015-- Gilead Sciences, Inc. (Nasdaq:GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved the use of Letairis (ambrisentan) in combination with tadalafil for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability. Letairis is an endothelin receptor antagonist that was first approved in 2007 in the U.S. as monotherapy for PAH to improve exercise ability and delay clinical worsening. Tadalafil is a PDE5 inhibitor that was initially approved for PAH in the U.S. in 2009 to improve exercise ability.

“The evidence to support the use of ambrisentan and tadalafil in PAH is well-established, however an outstanding question has been whether combining these two medications up front may further delay the progression of this disease over the long term for patients who are newly starting PAH therapy,” said Ronald J. Oudiz, MD, Professor of Medicine, David Geffen School of Medicine at UCLA and Director, Liu Center for Pulmonary Hypertension, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. “Based on the data supporting today’s approval, we now know that patients receiving ambrisentan and tadalafil up front are less likely to experience disease progression or be hospitalized, and have more improvement in exercise ability than patients receiving either effective therapy alone. As such, this combination represents a new treatment strategy for patients living with this debilitating and life-threatening disease.”

The new labeling is supported by data from the AMBITION study (a randomized, double-blind, multicenter study of first-line combination therapy with AMBrIsentan and Tadalafil in patients with pulmonary arterial hypertensION). In AMBITION, 605 patients with WHO Functional Class II or III PAH were randomized (2:1:1) to receive once-daily Letairis plus tadalafil (n=302) or to Letairis (n=152) or tadalafil (n=151) alone. Treatment was initiated with Letairis 5 mg and tadalafil at 20 mg. If tolerated, tadalafil was increased to 40 mg at four weeks and Letairis was increased to 10 mg at eight weeks. The primary endpoint was time to first occurrence of death, hospitalization for worsening PAH, greater than 15 percent decrease from baseline in six-minute walk distance (6MWD) combined with WHO Functional Class III or IV symptoms sustained over 14 days (short-term clinical worsening) or reduction in 6MWD sustained over 14 days combined with WHO Functional Class III or IV symptoms sustained over 6 months (inadequate long-term clinical response).

In the study, combination therapy with Letairis and tadalafil demonstrated superiority in reducing the risk of the composite primary endpoint by 49 percent and 45 percent, respectively, versus monotherapy with Letairis (hazard ratio = 0.51; 95 percent CI: 0.35, 0.73; p=0.0002) or tadalafil (hazard ratio = 0.55; 95 percent CI: 0.37, 0.81; p=0.002). Overall, 20 percent of patients receiving combination therapy experienced a primary endpoint event compared to 35 percent and 30 percent, respectively, in patients receiving Letairis or tadalafil.

Combination therapy also demonstrated a reduced risk of hospitalization for worsening PAH of 67 percent and 56 percent, respectively, compared to Letairis (hazard ratio = 0.33; 95 percent CI: 0.19, 0.55) or tadalafil (hazard ratio = 0.44; 95 percent CI: 0.25, 0.79). Overall, 8 percent of patients receiving combination therapy were hospitalized for worsening PAH compared to 22 percent and 15 percent, respectively, in patients receiving Letairis or tadalafil.

Patients receiving Letairis plus tadalafil also experienced statistically significant improvements from baseline in 6MWD versus individual monotherapy, with a median difference of 24 meters and 20 meters, respectively, from Letairis (95 percent CI: 11, 37; p=0.0004) or tadalafil (95 percent CI: 8, 32; p=0.0016) at Week 24.

When Letairis is used in combination with tadalafil, the common adverse reactions (>5 percent than on either monotherapy) were peripheral edema (Combination: 45 percent; Letairis: 38 percent; tadalafil: 28 percent), headache (Combination: 41 percent; Letairis: 34 percent; tadalafil: 35 percent), nasal congestion (Combination: 19 percent; Letairis: 16 percent; tadalafil: 11 percent), cough (Combination: 18 percent; Letairis: 13 percent; tadalafil: 16 percent), anemia (Combination: 15 percent; Letairis: 7 percent; tadalafil: 11 percent), dyspepsia (Combination: 11 percent; Letairis: 3 percent; tadalafil: 12 percent) and bronchitis (Combination: 10 percent; Letairis: 4 percent; tadalafil: 9 percent). Letairis has a labeled BOXED WARNING and an associated Risk Evaluation and Mitigation Strategy (REMS) program regarding the risk of embryo-fetal toxicity; see below for Important U.S. Safety Information for Letairis.

Data from AMBITION were published in The New England Journal of Medicine and Letairis plus tadalafil was the only recommended initial combination therapy option for PAH in the “2015 European Society of Cardiology / European Respiratory Society Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension” published in the European Heart Journal in August 2015.AMBITION was cosponsored by Gilead and GlaxoSmithKline (GSK). Eli Lilly and Company also provided funding and tadalafil drug supply for the trial. Gilead commercializes ambrisentan under the tradename Letairis in the U.S. and GSK commercializes ambrisentan under the tradename Volibris® in territories outside of the U.S.

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.

About Letairis

Letairis is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability and delay clinical worsening; and in combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability. Studies establishing effectiveness included predominantly patients with WHO Functional Class II-III symptoms and etiologies of idiopathic or heritable PAH (60 percent) or PAH associated with connective tissue diseases (34 percent).

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. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

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 possibility that physicians may not see the benefit of combination therapy with Letairis and tadalafil. 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 June 30, 2015, 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.

Source: Gilead Sciences, Inc.

Posted: October 2015

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