FDA approves combination drug to treat pulmonary arterial hypertension

The FDA approved the combination of ambrisentan and tadalafil to reduce the risks of disease progression and hospitalization for worsening pulmonary arterial hypertension (PAH) and improve exercise ability.

Ambrisentan, an endothelin receptor antagonist, was approved in 2007 as monotherapy to improve exercise ability and delay clinical worsening in patients with PAH. Tadalafil, a PDE5 inhibitor, was approved in 2009 to improve exercise ability in patients with PAH.

The approval of the combination medication from Gilead Sciences was based on results of the multicenter, randomized, double-blind AMBITION (Ambrisentan and Tadalafil in Patients with Pulmonary Arterial Hypertension) trial.

Between Oct. 18, 2010, and July 31, 2014, the researchers enrolled 605 patients with PAH at 120 centers in 14 countries. Patients were randomized to receive the combination of 10 mg of ambrisentan and 40 mg of tadalafil, 10 mg of ambrisentan plus placebo or 40 mg of tadalafil plus placebo.

The primary end point was the first event of clinical failure, which researchers defined as the first occurrence of a composite of death, hospitalization for worsening pulmonary arterial hypertension, disease progression or unsatisfactory long-term clinical response.

The primary end point occurred in 18 percent of the combination ambrisentan and tadalafil group, 34 percent of the ambrisentan group and 28 percent of the tadalafil group.

The following adverse events occurred more frequently in the combination ambrisentan and tadalafil group: peripheral edema, headache, nasal congestion, cough, dyspepsia, bronchitis and anemia.