6/29/23, 1:45 AM PULSAR (high-dose sotatercept) Pathway Feedback Search Clinical Topics Home Studies PULSAR (high-dose sotatercept) PULSAR (high-dose sotatercept) Disease Pulmonary hypertension Trial question What is the role of high-dose sotatercept in patients with pulmonary arterial hypertension? Study design Multi-center Double blinded RCT Population Characteristics of study participants 89.0% female N = 74 11.0% male 74 patients (66 female, 8 male) Inclusion criteria: adults who were receiving background therapy for pulmonary arterial hypertension Key exclusion criteria: portopulmonary disease; schistosomiasis; and human immunodeficiency virus infection-associated pulmonary arterial hypertension; portal hypertension or chronic liver disease Interventions N=42 high-dose sotatercept (subcutaneous dose of 0.7 mg/kg every 3 weeks for 24 weeks) N=32 placebo (matching placebo every 3 weeks for 24 weeks) Primary outcome https://web.pathway.md/studies/recPqob7kKfaVUKk8 1/2 6/29/23, 1:45 AM PULSAR (high-dose sotatercept) Pathway Pulmonary vascular resistance reduction at week 24 255.9 dyn s/ 255.9 191.9 dyn s/ 128.0 dyn s/ 64.0 dyn s/ Significant increase 16.4 0.0 dyn s/ High-dose sotatercept Placebo Significant increase in pulmonary vascular resistance reduction at week 24 (255.9 dyn s/cm vs. 16.4 dyn s/cm ; AD 239.5 dyn s/cm , 95% CI 149.7 to 329.3) Secondary outcomes No significant difference in improvement in 6-minute walk distance at week 24 (50.1 m vs. 28.7 m; AD 21.4 m, 95% CI -2.8 to 45.7) Significant increase in N-terminal pro-BNP level reduction at week 24 (340.6 pg/mL vs. -310.4 pg/mL; AD 651 pg/mL, 95% CI 258.7 to 1043.3) Significant increase in reduction in systolic excursion from the tricuspid annular plane at week 24 (AD 0.1 cm, 95% CI 0.08 to 0.2) Safety outcomes No significant difference in any adverse event. Significant difference in thrombocytopenia (12% vs. 0%). Conclusion In adults who were receiving background therapy for pulmonary arterial hypertension, high-dose sotatercept was superior to placebo with respect to pulmonary vascular resistance reduction at week 24. Reference Marc Humbert, Vallerie McLaughlin, J Simon R Gibbs et al. Sotatercept for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2021 Apr 1;384(13):1204-1215. Open reference URL https://web.pathway.md/studies/recPqob7kKfaVUKk8 2/2