About Actelion-1

Actelion-1 is a highly potent, tissue-targeting endothelin receptor antagonist discovered in an in-house research program. Through complete blockade of tissular endothelin, Actelion-1 is expected to protect tissue from the damaging effect of elevated endothelin, specifically in the cardiovascular system. In pre-clinical studies, Actelion-1 also exhibited effects suggesting that it maintains the integrity of the vascular wall and improves long-term outcome. Accordingly, Actelion-1 may provide therapeutic benefit in a wide range of cardiovascular indications.

Current Status

Actelion-1 is currently investigated in the phase III study SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome). This study is designed to evaluate the safety and efficacy of Actelion-1 in delaying disease progression and mortality in patients with pulmonary arterial hypertension (PAH).

SERAPHIN is a global study and will enroll more than 500 patients from at least 180 centers, randomized 1:1:1 to receive two different doses of Actelion-1 (3 mg and 10 mg once daily) or placebo. The centers represent over 40 countries in North and South America, Europe, Asia Pacific and Africa.

SERAPHIN will evaluate the clinical benefit of Actelion-1 through the primary endpoint of morbidity and all-cause mortality in patients with symptomatic PAH.

Supporting Studies

In a phase II study with 379 hypertensive patients, Actelion-1 was significantly better than placebo and better than enalapril in reducing blood pressure 24 hours after drug intake. In this patient population, Actelion-1 was generally well tolerated. The overall frequency of adverse events was similar to those observed in the placebo group. Similar to other endothelin receptor antagonists, Actelion-1 may potentially exhibit known class effects such as a propensity for elevated liver enzymes, which will be monitored in the SERAPHIN study. Additional interaction studies concluded prior to the start of the SERAPHIN study have shown no clinically relevant interaction with warfarin, sildenafil, or ketoconazole.