FDA Approves Ambrisentan (Letairis) for Pulmonary Arterial Hypertension

ROCKVILLE, Md., June 18 -- The FDA has approved ambrisentan (Letairis), an endothelin receptor antagonist, for pulmonary arterial hypertension (PAH).

The drug, which will be marketed as 5 mg and 10 mg tablets for once daily treatment of PAH, received expedited review as an orphan drug.

John Jenkins, M.D., director of FDA's Office of New Drugs, said ambrisentan is similar to bosentan (Tracleer), which is already approved for PAH but ambrisentan "offers the potential for fewer drug interactions." Patients taking ambrisentan must have monthly blood tests to check for potential liver injury.

The safety and effectiveness of ambrisentan were demonstrated in two randomized, double-blind, 12-week, placebo-controlled phase III clinical trials (ARIES-1 and ARIES-2) that enrolled 393 patients.

In ARIES-1 patients treated with 5 mg of ambrisentan increased six-minute-walk distance by a mean of 31 meters and a median of 27 meters compared with baseline (P =0.008). The 10-mg dose was associated with a mean increase of 51 meters and a median increase of 39 meters (P<0.001).

In ARIES-2, placebo-adjusted mean and median changes from baseline of 59 meters and 45 meters (P< 0.001) were observed with the 5-mg dose.

Ambrisentan also significantly delayed time to clinical worsening of PAH, defined as death, lung transplantation, hospitalization for PAH, atrial septostomy, study withdrawal because of the addition of other PAH therapeutic agents, or study withdrawal because of early escape (progressive disease).

The most common side effects from ambrisentan, said the FDA, included swelling of legs and ankles, nasal congestion, sinusitis, and getting red in the face (flushing).

Ambrisentan should not be used by women who are pregnant or may become pregnant because the drug may cause birth defects.

Ambrisentan is manufactured by Gilead Sciences.