Gilead’s Letairis with Tadalafil Approved by FDA for Pulmonary Arterial Hypertension

Gilead Sciences announced that the U.S. Food and Drug Administration (FDA) has approved Letairis^® (ambrisentan) with tadalafil for pulmonary arterial hypertension (PAH) to diminish disease progression risk and hospitalization and to improve the ability to exercise — a decision that directly follows recent study results indicating the efficacy of the combination therapy in PAH patients. Letairis was initially approved in 2007 in the United States for PAH to improve the ability to exercise ability and to delay PAH symptoms from getting worse. Tadalafil was first approved for PAH in the U.S. in 2009 to improve the ability to exercise.

PAH refers to high blood pressure of the lungs. It is a condition that worsens over time and can be potentially fatal, since pressure in the lung arteries can strain the heart. Although PAH currently has no cure, several medications are used to control symptoms.

The AMBITION study supported the approval of the combination therapy. Data from AMBITION were published in The New England Journal of Medicine.

The study was conducted by Nazzareno Galié, MD and colleagues at the Department of Experimental, Diagnostic and Specialty Medicine at the University of Bologna, Italy. For the AMBITION study, 605 patients were administered a combination therapy of ambrisentan/tadalafil, ambrisentan monotherapy, or tadalafil monotherapy. The study’s primary endpoint was time to death, hospitalization for PAH worsening, greater than 15 percent decrease from baseline in six-minute walk distance combined with short-term clinical worsening or reduction in 6-minute walk over 14 days combined with inadequate long-term clinical response.

Combination therapy with ambrisentan and tadalafil was superior for reducing the risk of the primary endpoint by 49 percent versus ambrisentan alone or 45 percent tadalafil. Overall, 20 percent of individuals who received combination therapy experienced a primary endpoint event compared to 35 percent and 30 percent, respectively, in those people who received ambrisentan or tadalafil.

“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,” noted 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.”