GSK announced publication of the AMBITION study, the first outcomes study to compare the safety and efficacy of investigational first-line combination therapy of Volibris® (ambrisentan) and Adcirca® (tadalafil) to first-line monotherapy of either treatment alone in treatment-naïve patients with pulmonary arterial hypertension (PAH).
The AMBITION study was a randomised, double-blind Phase 3b/4 study designed to compare the efficacy and safety of ambrisentan in combination with tadalafil to monotherapy in treatment-naïve patients with WHO/NYHA functional class II and III PAH. In the study, 500 patients were randomised (2:1:1) to receive ambrisentan and tadalafil combination (n=253) or monotherapy with ambrisentan (n=126) or tadalafil (n=121) (titrated from 5 mg to 10 mg once-daily and from 20 mg to 40 mg once-daily for ambrisentan and tadalafil, respectively). The AMBITION study was co-sponsored by GSK and Gilead. Eli Lilly and Company also provided funding and tadalafil drug supply for the study.
The primary endpoint was time to first clinical failure event, defined as time from randomisation to the first occurrence of death (all-cause), hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response (events adjudicated by an independent, blinded committee). Results of the AMBITION study were first presented at the European Respiratory Society congress in September 2014.
Ambrisentan, a selective endothelin type-A receptor antagonist, and tadalafil, a PDE-5 inhibitor, are each approved in the EU and other countries as once-daily treatments for PAH, (WHO Group 1) in patients with WHO/NYHA functional class II and III symptoms. GSK commercialises ambrisentan under the tradename Volibris® in territories outside of the United States and Gilead commercialises ambrisentan under the tradename Letairis® in the U.S. Ambrisentan has been granted orphan drug status for the treatment of PAH in Australia, Europe, Japan, Korea and United States. GSK also has an exclusive license from Eli Lilly and Company to promote tadalafil for PAH under the tradename Adcirca® in Europe.
