Gilead Sciences announced results from the Phase 3 AMBITION (AMBrIsentan and Tadalafil in patients with pulmonary arterial hypertensION) study.
AMBITION was a randomized, double-blind study designed to compare the safety and efficacy of investigational first-line combination therapy (ambrisentan and tadalafil) to first-line monotherapy (ambrisentan or tadalafil) in patients with WHO/NYHA functional class II and III pulmonary arterial hypertension (PAH). Patients (n=500) were randomized (2:1:1) to receive ambrisentan and tadalafil (n=253) or monotherapy with ambrisentan (n=126) or tadalafil (n=121) (titrated from 5mg to 10mg once-daily and from 20mg to 40mg once-daily for ambrisentan and tadalafil, respectively). The primary endpoint was time to first clinical failure event, defined as time from randomization to the first occurrence of death (all-cause), hospitalization for worsening PAH, disease progression or unsatisfactory long-term clinical response.
Treatment with the combination of ambrisentan 10mg and tadalafil 40mg reduced the risk of clinical failure by 50% compared to the pooled ambrisentan and tadalafil monotherapy arm (HR=0.502; 95%CI: 0.348, 0.724; P=0.0002). The combination was also statistically significant vs. the individual ambrisentan and tadalafil monotherapy groups for the primary endpoint (P<0.01). The treatment effect observed with the primary endpoint was mainly driven by a reduction in hospitalizations. Time to first hospitalization was reduced by 63% (HR=0.372; 95% CI: 0.217, 0.639; P=0.0002).
Letairis (ambrisentan), a selective endothelin type-A receptor antagonist is already approved for the treatment of PAH (WHO Group 1), in patients with WHO/NYHA functional class II and III symptoms to improve exercise ability and delay clinical worsening. Adcirca (tadalafil; Eli Lilly and Company), a PDE5 inhibitor is also approved for PAH (WHO Group 1) to improve exercise ability.
Gilead plans to submit a supplemental new drug application (sNDA) to the FDA based on data from the AMBITION study by the end of this year.
For more information call (800) 445-3235 or visit Gilead.com.