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

Summary

In a phase 3 randomized trial of advanced, high-risk PAH on maximal background therapy, add-on sotatercept reduced the composite of death, lung transplantation, or ≥24-hour hospitalization versus placebo (17.4% vs 54.7%; HR 0.24). Adverse events included epistaxis and telangiectasia.

Key Findings

• Primary composite of death/transplant/≥24h hospitalization was reduced: 17.4% vs 54.7% (HR 0.24, 95% CI 0.13–0.43).
• Reductions were consistent across components: death 8.1% vs 15.1%, transplantation 1.2% vs 7.0%, hospitalization 9.3% vs 50.0%.
• Most common adverse events with sotatercept were epistaxis and telangiectasia.

Clinical Implications

Sotatercept can be considered as add-on therapy for high-risk PAH patients on maximal background therapy, with monitoring for epistaxis and telangiectasia and ongoing safety surveillance.

Limitations

• Trial stopped early, which may overestimate effect size and limits long-term safety assessment.
• Sample size (n=172) limits subgroup analyses and rare adverse event detection.

Future Directions

Long-term safety and durability of benefit, optimal sequencing with other PAH therapies, and real-world effectiveness in broader populations warrant study.