The 6th PVRI Annual Drug Discovery & Development Symposium for Pulmonary Hypertension was held on 1-2 July 2019 in Paris, France. It brought together undisputed leaders from clinical and translational pulmonary vascular research, industry representatives and members of the European Medicines Agency. The conference focused on Phase 2 clinical trials in the modern PAH management era.
Fourteen medications targeting the endothelin, nitric oxide and prostacyclin pathways have been approved for PAH in the last 25 years. However, in the last five years, the most important recent advance in PAH medical management have not been related to the discovery of novel drugs or pathways, but to the development of better strategies with an emphasis on early combination therapy and escalation of treatments based on systematic assessment of clinical response using a multiparametric risk stratification approach.
In that context, the current treatment algorithm provides the most appropriate initial strategy, including monotherapy or, more often, initial combination therapy. Further treatment escalation is required in case low-risk status is not achieved in planned follow-up assessments. In the modern management era, many PAH patients are doing well while on therapy. However, a number of patients still do not reach the treatment goals with double or triple combination therapy and there is a clear unmet need to develop novel strategies and target novel pathways.
The event was a great success, with excellent conferences and discussions between presenters, moderators, and attendees. There were many highlights, including a keynote lecture describing drug development in PAH since the early days of pure vasodilator therapies to the recent age of multiple approved agents targeting the three pathways. There was also a good analysis of a series of recent negative phase 2 clinical trials and a discussion on the best use of animal models for drug development. There were interesting talks on better use of surrogate endpoints and biomarkers and lessons from heart failure colleagues on how to develop creative strategies to improve success in Phase 2 trials.
Further discussions focused on what to do when the primary endpoint of a study fails and whether responder and non-responder analyses can help us in negative clinical trials, with the examples of tocilizumab and imatinib studies in PAH. Current clinical trials targeting novel pathways were then presented with enthusiasm by different investigators (PARP-1 inhibition, ifetroban, sotatercept, dopamine ß monooxygenase inhibitor). The conference closed with a superb presentation on pulmonary artery denervation in PAH with a device-based approach.
After such a nice event, we look forward to the next PVRI Drug Discovery & Development Symposium, which will be held in Boston in July 2020. See you there!