Have Your Voice Heard During a Special Debate on Issues Related to Clinical Trials for Pulmonary Arterial Hypertension.

Currently there have been seven drugs approved for the chronic treatment of pulmonary arterial hypertension (PAH). Yet, because of the use of similar trial design and endpoints, questions remain about the longterm benefits, effects on survival, and mechanism of action of these agents, as well as the appropriate trial design. Join regulatory, industry, and academic leaders as they debate the uncertainties around the approved treatments for PAH, alternative clinical trial designs for future studies that better address the unanswered questions from the existing trials, and limitations in performing clinical trials in patients with PAH.

Debate Topics
• A minimum change in six minute walk (6MW) needs to be established as an indicator of efficacy in future trials
vs.
• Any significant change in 6MW remains an adequate primary endpoint of efficacy

• Survival needs to be a primary endpoint in future randomized clinical trials (RCTs) until long-term improved survival is demonstrated
vs.
• Composite endpoints are adequate surrogates for survival

• Future trials need to identify specific etiologies of PAH and to power the trials sufficiently to know in which etiologies treatment is effective
vs.
• Approval of drugs (i.e., WHO Group I) for PAH is appropriate for all patients

• The prescription of PAH therapies should continue to be linked to a patient’s functional class
vs.
• Functionl class should not be a determinant of which patients are studied and which patients are treated in RCTs

• Future RCTs with antiproliferative therapies must include both traditional endpoints and endpoints with biomarker/imaging techniques to demonstrate mechanisms of efficacy
vs.
• Clinical endpoints are adequate to determine efficacy of newer therapies

• Future trials of PAH that characterize patients by biologic pathways may receive provisional approval for subsets of patients (i.e., approval under Subpart H) even if the overall study cohort does not demonstrate a clinically meaningful difference
vs.
• PAH should be considered a single disease and established principles dictate that drugs need to have a significant clinical benefit overall