Gilead Reports Ambrisentan, Tadalafil Combo Better In PAH Than Monotherapy

By Cyndi Root

Gilead Sciences announced in a press release that a study of ambrisentan and tadalafil showed that the combination treatment worked better than either drug alone. The AMBITION study, conducted with GlaxoSmithKline with funding and tadalafil drug supply from Eli Lilly, evaluated the drugs in patients with pulmonary arterial hypertension (PAH). Gilead plans to present its findings at the ERS International Congress 2014, the annual meeting of the European Respiratory Society.

Gilead intends to use the data in a supplemental New Drug Application (sNDA) to the Food and Drug Administration (FDA) by the end of 2014, as the combination use is not yet approved. Norbert Bischofberger, PhD, Gilead’s EVP of Research and Development and CSO, said, “We are pleased that the combination of ambrisentan and tadalafil has resulted in a clinically meaningful benefit for PAH patients.”

Ambrisentan And Tadalafil

Ambrisentan is a selective endothelin type-A receptor antagonist. Tadalafil is a PDE5 inhibitor. They are both approved in the U.S., the EU, and other countries for monotherapy in patients with PAH. The drugs can also delay clinical worsening and to increase exercise capacity. Due to preclinical data showing synergistic effects, Gilead, GSK, and Eli Lilly designed a trial to test the combination therapy vs. the monotherapy.

Lewis J. Rubin, MD, Emeritus Professor, University of California, San Diego and Co-Chair of the AMBITION Steering Committee, stated that the PAH community has long been interested in combination therapies. He said, “The majority of combination studies to date have evaluated add-on combination treatment approaches with mixed results.”

AMBITION Trial

The AMBITION trial, however, did not show mixed results. Instead, it showed a 50 percent reduction in risk of clinical failure in using ambrisentan and tadalafil together in the treatment of PAH. The efficacy and safety study randomized 500 patients with WHO/NYHA functional class II and III PAH into combination therapy or monotherapy treatment arms. Patients on combination therapy saw a 63 percent reduction in the incidence of hospitalization. Safety issues were relatively the same in the treatment arms, although combination therapy patients experienced peripheral edema, headache, nasal congestion, and anemia more frequently.