PURPOSE:To evaluate the effects of chronically administered inhaled treprostinil (TRE), a prostacyclin analogue, over 24 months on both exercise capacity and safety in patients with severe PAH.
METHODS:Open label, continuation study evaluating inhaled TRE (up to 72 μg four times daily) over 24 months in patients who successfully completed the TRIUMPH-1 study. Efficacy endpoints including exercise capacity (6MWD), change in NYHA class, and Quality of Life (MLWHF) were assessed every 3 months. Safety endpoints included clinical chemistry, hematology and adverse events.
RESULTS:206 patients (125 US, 81 Rest of World) enrolled at 30 centers. Baseline characteristics included mean age of 53.6 years with 56% idiopathic PAH, and 11%, 86% and 3% NYHA class II, III and IV, respectively. Baseline 6MWD (mean ± SD) was 349 ± 81 meters with 143 patients receiving bosentan and 63 receiving sildenafil. Median 6MWD significantly improved 28 (n=156), 31 (n=88), 34 (n=50), and 50m (n=17) at months 6, 12, 18 and 24, respectively. Significant improvements in MLWHF global, physical and emotional scores were observed. Currently, 146 patients are ongoing; discontinuations include death (7), disease progression (11), adverse events (27), withdrawal of consent (10) and other (5). There were no clinically significant changes in clinical chemistry or hematology. The most frequent AEs reported were cough, headache and nausea occurring in 54, 38 and 21% of patients, respectively.
CONCLUSION:Inhaled TRE provides incremental benefit to patients currently receiving oral therapies for PAH over 24 months, and offers several advantages including patient convenience, targeted drug delivery, and a favorable systemic safety profile.
CLINICAL IMPLICATIONS:Inhaled TRE represents a potential new additional therapy for patients with PAH on oral monotherapy.
DISCLOSURE:R Benza, Grant monies (from industry related sources) Research grants and honoraria from Gilead, United Therapeutics, Actelion and Encysive.; No Product/Research Disclosure Information