Gilead Sciences announced that the Food and Drug Administration (FDA) has approved Letairis (ambrisentan) in combination with tadalafil for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1).
The approval is based on data from the AMBITION study, a randomized, double-blind, multicenter study of Letairis and tadalafil as a first-line treatment in patients with PAH. In the study, 605 patients with WHO Functional Class II or III PAH received Letairis 5mg plus tadalafil 20mg, Letairis 5mg alone, or tadalafil 20mg alone. If tolerated, tadalafil was increased to 40mg at four weeks and Letairis to 10mg 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 six months (inadequate long-term clinical response).
Patients receiving Letairis plus tadalafil had a lower risk of the composite primary endpoint by 49% and 45%, respectively, vs. monotherapy with Letairis or tadalafil. A total of 20% of patients receiving combination therapy experienced a primary endpoint event vs. 35% and 30%, respectively, in patients receiving Letairis or tadalafil. The combination therapy also demonstrated a reduced risk of hospitalization for worsening PAH of 67% and 56%, respectively, compared to Letairis or tadalafil and 8% of patients receiving combination therapy were hospitalized for worsening PAH compared to 22% and 1%, respectively, in patients receiving Letairis or tadalafil. The Letairis plus tadalafil arm also experienced statistically significant improvements from baseline in 6MWD vs. individual monotherapy at Week 24.
Letairis, a selective endothelin type-A receptor antagonist, and tadalafil, a PDE-5 inhibitor, were already approved as monotherapies for patients with PAH (WHO Group 1) with WHO/NYHA Functional Class II and III symptoms.
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