Abstract
Pulmonary arterial hypertension (PAH) is characterized by an increase in pulmonary vascular resistance ultimately resulting in progressive right heart failure. Although new specific treatments have demonstrated improvements in various end points including morbidity/mortality, prognosis remains unfavorable with an on-treatment yearly mortality rate of 10%. Due to complex delivery systems, the use of parenteral prostanoids has been limited to patients with advanced disease. While inhaled prostanoids have had little effect, an oral prostacyclin analog is a desired initial treatment for PAH patients. To that end, UT-15C was synthesized as a sustained-release tablet. FREEDOM-M in treatment-naïve PAH patients resulted in significant improvements of 6-min walk distance supporting the use of oral treprostinil as initial monotherapy in PAH patients with class II or III symptoms. A further study targeting patients on combination treatments is currently exploring a morbidity/mortality end point in a large patient population.
Financial & competing interests disclosure
N Skoro-Sajer has received financial sponsorship from United Therapeutics, Actelion, AOP Orphan, Pfizer and GSK. I Lang has received financial sponsorship from Uni-tiech Pharmaceutical, AOP Orphan, Bayer Healthcare, Pfizer, Actelion, GSK and has received grants from Actelion, Bayer HealthCare and AOP Orphan. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Key issues
Due to complex delivery systems, the use of parenteral prostanoids has been limited to patients with advanced disease or no-option.
While inhaled prostanoids have been less effective, an oral prostacyclin analog is a desired initial treatment for pulmonary arterial hypertension (PAH) patients.
Oral treprostinil showed no impact on exercise capacity of PAH patients stable on background therapy in FREEDOM-C and FREEDOM-C2 studies.
FREEDOM-M resulted in significant improvements of 6MWD in treatment-naïve PAH patients treated with oral treprostinil for 12 weeks.
Oral treprostinil provides an initial treatment option for PAH patients with less severe disease (FC II-III).