New therapeutic targets: moving form pre-clinical data to phase 2 studies

“Despite the success of these drugs in improving the wellbeing of our patients, we feel that we can do better”, said Prof. Martin Wilkins (Imperial College London, UK) at the beginning of his lecture. “The ultimate goal is to stop disease progression and, if possible, reverse the remodelling that characterises PAH. The problem is that we lack knowledge about the interplay between these pathways in the remodelling process. The good news is that we have a number of druggable targets in each of these pathogenic mechanisms (see Table). The real challenge is to prioritise and identify which of these candidate drugs might offer the most rapid progress.”

Many of these drugs have entered clinical trials. However, only prostacyclin analogues have reached the phase 3 stadium.

Table: Overview of several drug targets in PAH



Five key aspects

In selecting the optimal therapy 5 aspects are important according to Prof. Wilkins: the right target, the right tissue, the right safety, the right patient, and the right commercial potential.

“We cannot overemphasise the importance of a valid target. Selecting the right target remains the most important of the 5 aspects and the most important decision we make in drug development.”