Sotatercept for Pulmonary Arterial Hypertension within the First Year after Diagnosis.

Summary

In a multicenter phase 3 RCT of 320 adults with PAH diagnosed within the prior year, add-on sotatercept reduced time to clinical worsening versus placebo (HR 0.24) on top of double/triple background therapy. Benefits were driven by fewer exercise test deteriorations and PAH hospitalizations; adverse events included epistaxis and telangiectasia.

Key Findings

• Primary endpoint events: 10.6% with sotatercept vs 36.9% with placebo (HR 0.24; 95% CI 0.14–0.41; P<0.001).
• Exercise test deterioration: 5.0% vs 28.8%; unplanned PAH hospitalization: 1.9% vs 8.8% (sotatercept vs placebo).
• Adverse events: epistaxis (31.9%) and telangiectasia (26.2%) were most common with sotatercept.

Clinical Implications

For PAH within one year of diagnosis, consider adding sotatercept to optimized background therapy in WHO FC II–III with intermediate/high risk, with monitoring for epistaxis/telangiectasia and hematologic effects. Earlier initiation may reduce hospitalizations and functional decline.

Limitations

• Early trial termination may overestimate effect size and limits long-term safety assessment.
• Mortality events were few and similar across groups; no atrial septostomy or transplantation occurred.

Future Directions

Assess long-term outcomes, optimal sequencing with other PAH therapies, and real-world effectiveness/safety in broader populations including WHO FC IV. Explore biomarkers to guide sotatercept initiation.