Letairis (ambrisentan) is a potent type-A selective endothelin receptor antagonist. Endothelin is a peptide made by the body in the endothelium. It constricts blood vessels and elevates blood pressure. Endothelin receptor antagonists (ETRAs) are a class of drugs which prevent the constriction or narrowing of blood vessels thereby enhancing blood flow throughout the body.
Letairis is specifically indicated for the treatment of pulmonary arterial hypertension in subjects with WHO class II or III symptoms to improve exercise capacity and delay clinical worsening.
Letairis is supplied as a 5 mg or 10 mg tablet designed for oral administration. The recommended initial dose of the drug is 5 mg once daily. The dose may be increased to 10 mg once daily if the 5 mg dose is tolerated.
FDA approval of Letairis was based on the results of two clinical trials. These 12-week, randomized, double-blind, placebo-controlled, multicenter studies were dubbed ARIES-1 and ARIES-2.
Subjects in this trial received once-daily doses of Letairis (5 mg and 10 mg) or placebo. The primary endpoint was the change from baseline in the 6-minute walk distance. The mean change from baseline in the 5 mg group was 23 ± 83, in the 10 mg group 44 ± 63 versus -8 ± 79 in the placebo group. The placebo-adjusted mean change from baseline was 31 meters in the 5 mg group and 51 meters in the 10 mg group (p=0.008 and p=<0.001, respectively). The time to clinical worsening occurred in 10% of the placebo group compared to 3% of the Letairis group.
Subjects in this trial received once-daily doses of Letairis (2.5 mg and 5 mg) or placebo. Again the primary endpoint was the change from baseline in the 6-minute walk test. The mean change from baseline in the 2.5 mg group was 22 ± 83, in the 5 mg group 49 ± 75 versus -10 ± 94 in the placebo group. The placebo-adjusted mean change from baseline was 32 meters in the 2.5 mg arm and 59 meters in the 5 mg arm (p=0.022 and p=<0.001, respectively). The time to clinical worsening occurred in 22% of the placebo group compared to 6% of the Letairis group.
In addtion Letairis was evaluated in an open-label long-term follow-up trial. The trial followed 383 subjects who had been previously been treated in ARIES-1 and ARIES-2. Results showed that 95% were still alive after one year and 94% were still receiving Letairis monotherapy.
Ongoing Study Commitments
Adverse events associated with the use of Letairis may include, but are not limited to, the following:
Letairis (ambrisentan) is a potent type-A selective endothelin receptor antagonist. Endothelin is a peptide made by the body in the endothelium and it constricts blood vessels and elevates blood pressure. There are two classes of endothelin receptors: Endothelin A (ET-A) and Endothelin B (ET-B). The binding of endothelin to ET-A receptors causes vasoconstriction while the binding to ET-B causes vasodilatation. Ambrisentan is a high affinity ET-A receptor antagonist with a high selectivity for the ET-A versus ET-B receptor.
Barst RJVascular Health and Risk Management 2007;3(1):11-22.
Vatter H, Seifert V Ambrisentan, a non-peptide endothelin receptor antagonist. Cardiovascular Drug Reviews 2006 Spring;24(1):63-76
Galié N, Badesch D, Oudiz R, Simonneau G, McGoon MD, Keogh AM, Frost AE, Zwicke D, Naeije R, Shapiro S, Olschewski H, Rubin LJ Ambrisentan therapy for pulmonary arterial hypertension. Journal of the American College of Cardiology 2005 Aug 2;46(3):529-35
Channick RN, Sitbon O, Barst RJ, Manes A, Rubin LJ Endothelin receptor antagonists in pulmonary arterial hypertension. Journal of the American College of Cardiology 2004 Jun 16;43(12 Suppl S):62S-67S
For additional information regarding Letairis or pulmonary arterial hypertension, please visit the Letairis web page.