Sotatercept for the Treatment of Pulmonary Arterial Hypertension (STELLAR)

Existing PAH therapies target vasodilation (endothelin, NO, and prostacyclin pathways) but do not address the underlying vascular remodeling. Sotatercept is an activin signaling inhibitor (ActRIIA-Fc fusion protein) that targets the TGF-β superfamily to reverse vascular remodeling — a completely new mechanism.

Multicenter RCT (n=163) comparing sotatercept (0.7 mg/kg SC every 3 weeks) vs. placebo added to background PAH therapy over 24 weeks.

Sotatercept significantly improved 6-minute walk distance (+34.4 m vs −1.6 m, p<0.001), reduced PVR (−163.9 vs +11.5 dyn·s·cm⁻⁵), and improved WHO functional class. Also reduced risk of clinical worsening.

Sotatercept (Winrevair) was FDA-approved in 2024 for PAH — the first drug with a truly novel mechanism in over 20 years. It is used as add-on therapy to background PAH treatment. Represents a paradigm shift from vasodilation to vascular remodeling reversal.

Short 24-week trial. Long-term mortality data pending. Subcutaneous injection every 3 weeks. Cost and access may be barriers.