Real-World Sotatercept Eligibility: Analysis from the FOCUS-PAH Registry

Area of Science:

• Cardiology
• Pulmonary Medicine
• Clinical Trials

Background:

• Pulmonary arterial hypertension (PAH) has poor outcomes despite current treatments.
• Sotatercept shows promise but trial criteria may restrict its real-world use.

Purpose of the Study:

• To assess real-world eligibility for sotatercept trials (STELLAR/ZENITH) at baseline and follow-up.
• To identify predictors of non-eligibility in PAH patients.

Main Methods:

• Retrospective analysis of 541 PAH patients meeting inclusion criteria (WHO FC II/III, PVR ≥5 WU, stable therapy).
• Eligibility assessed against STELLAR criteria and extended using ZENITH criteria.
• Multivariable models identified predictors of non-eligibility.

Main Results:

• 19% of patients were ineligible at baseline, primarily due to PAH subtype or vasoreactivity.
• Cumulative eligibility during follow-up was 50%, with PVR <5 WU or therapy changes being common exclusion reasons.
• Older age and triple therapy predicted non-eligibility; idiopathic PAH was protective. ZENITH criteria increased eligibility by 6%.

Conclusions:

• STELLAR trial criteria exclude a significant number of real-world PAH patients, especially during follow-up.
• ZENITH criteria offer only a modest improvement in eligibility.
• Optimized patient selection and timing are crucial for sotatercept's real-world application in PAH.