Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension

This double-blind, phase 3 trial (STELLAR) evaluated sotatercept, a ligand trap targeting activins and growth differentiation factors in 323 adults with pulmonary arterial hypertension (PAH) (WHO functional class II or III) on stable background therapy. Participants were randomized to receive subcutaneous sotatercept or placebo every 3 weeks. At week 24, the median change in 6-minute walk distance was 34.4 m (sotatercept) vs. 1.0 m (placebo), with a Hodges-Lehmann estimate of +40.8 m (P<0.001). Eight secondary endpoints showed significant improvement with sotatercept: multicomponent clinical improvement, reduced pulmonary vascular resistance, lowered NT-proBNP, improved WHO functional class, decreased clinical worsening events, increased French low-risk status, and better quality-of-life scores (PAH-SYMPACT Physical and Cardiopulmonary domains). Common adverse events included epistaxis, dizziness, telangiectasia, elevated hemoglobin, thrombocytopenia, and hypertension. Sotatercept demonstrated robust efficacy and manageable safety, potentially introducing a new therapeutic class for PAH.

This double-blind, phase 3 trial (STELLAR) evaluated sotatercept, a ligand trap targeting activins and growth differentiation factors in 323 adults with pulmonary arterial hypertension (PAH) (WHO functional class II or III) on stable background therapy. Participants were randomized to receive subcutaneous sotatercept or placebo every 3 weeks. At week 24, the median change in 6-minute walk distance was 34.4 m (sotatercept) vs. 1.0 m (placebo), with a Hodges-Lehmann estimate of +40.8 m (P<0.001). Eight secondary endpoints showed significant improvement with sotatercept: multicomponent clinical improvement, reduced pulmonary vascular resistance, lowered NT-proBNP, improved WHO functional class, decreased clinical worsening events, increased French low-risk status, and better quality-of-life scores (PAH-SYMPACT Physical and Cardiopulmonary domains). Common adverse events included epistaxis, dizziness, telangiectasia, elevated hemoglobin, thrombocytopenia, and hypertension. Sotatercept demonstrated robust efficacy and manageable safety, potentially introducing a new therapeutic class for PAH.