Pulmonary arterial hypertension (PAH) is the most serious and potentially devastating chronic disorder of the pulmonary circulation. It is a progressive and lethal disease, which is characterised by abnormally high blood pressure in the blood vessels which supply the lungs. The symptoms of PAH are non-specific. Shortness of breath is present in most PAH patients at the time of presentation. Exercise intolerance is a frequent complaint and, in most PAH patients, it has an insidious onset.

Estimates of the annual incidence of primary PAH range from 1-2 cases per million people with a prevalence of 136.000 patients in major markets. Considering the rarity and subtle presentation of this disease, correct diagnosis and reporting makes calculation of a true incidence difficult.

Currently approved therapeutic classes include prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors. They target specifically distinct molecular pathways, which are affected in PAH. From a market perspective PAH is considered a maturing market with market volume of 2nd generation drugs exceeding USD 100 Mio peak sales.

Using optimised dosing regimens, administration of these drugs results in moderate clinical benefits on exercise capacity and hemodynamics. However, in the predominant number of patients disease stabilisation is achieved only for a limited period of time and delaying, rather than stopping disease progression or even regression of disease is observed. The involvement and the contribution of other independent aberrations in metabolism and signalling pathways in the manifestation and progression of PAH are the likely explanation for this limited efficacy. They also form the rationale for the search and development of new therapeutic options.