Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk for Death.

Summary

In a phase 3 trial of 172 high-risk PAH patients on maximal background therapy, add-on sotatercept reduced the composite of death, transplant, or PAH-related hospitalization by 76% versus placebo (HR 0.24). The trial stopped early for efficacy; epistaxis and telangiectasia were the most common adverse events.

Key Findings

• Primary composite endpoint occurred in 17.4% with sotatercept vs 54.7% with placebo (HR 0.24, 95% CI 0.13–0.43).
• Reductions were seen across components: death (8.1% vs 15.1%), lung transplant (1.2% vs 7.0%), and hospitalization for PAH worsening (9.3% vs 50.0%).
• Trial stopped early at interim due to efficacy; epistaxis and telangiectasia were the most frequent adverse events.

Clinical Implications

Consider sotatercept as add-on therapy for WHO FC III/IV PAH patients at high 1-year risk despite optimized background therapy, with monitoring for epistaxis and telangiectasia.

Limitations

• Early stopping may overestimate effect size and limits long-term safety data.
• Modest sample size (n=172) and industry sponsorship may introduce biases.

Future Directions

Longer-term follow-up for survival and right heart remodeling, head-to-head or combination studies, and evaluation in broader PAH phenotypes.