Evolving Science of PAH Treatment

Program Goals

Paradigm Shift in PAH Treatment

Earlier PAH Clinical Trials

6-Minute Walk Test

Meta-Analysis of 22 RCTs

Changes in PAH Trials Over Time

Spectrum of PAH Double-Blind RCTs to Date Study Durations and Sizes

PAH Clinical Trials Evaluating Morbidity and Mortality Endpoints

Clinical Efficacy/Safety SERAPHIN Trial[a,b]

Clinical Efficacy/Safety GRIPHON Trial

GRIPHON: Primary Composite Endpoint

SERAPHIN Placebo vs Macitentan 3 mg vs Macitentan 10 mg (1:1:1)

Treatment Algorithm for PAH

Rationale for Combination Therapy

Expert Consensus Recommendations for Combination Therapy Have Improved With Increasing Experience

An Evolving Paradigm From Sequential to Initial Up-Front Combination Therapy

Case Study 29-Year-Old Woman, Referred for Abnormal Echocardiogram May 2015

Case Study (cont)

Case Study (cont)

Treatment Goals

Case Study (cont) Plan

Case Study (cont)

Case Study Intensification of Therapy?

Conclusion

Abbreviations

Abbreviations (cont)

Abbreviations (cont)

Abbreviations (cont)