The ZENITH trial tested sotatercept — an activin receptor fusion protein — added onto maximum background therapy in 172 adults with high-risk pulmonary arterial hypertension (WHO class III/IV). The trial was halted early due to striking efficacy: only 17.4% of sotatercept patients experienced a primary endpoint event (death, lung transplant, or worsening-related hospitalization) versus 54.7% on placebo — a 76% relative risk reduction. Deaths occurred in 8.1% vs 15.1%, and hospitalizations for worsening PAH in 9.3% vs 50%. Side effects included epistaxis and telangiectasia. These results suggest sotatercept offers a major therapeutic advance even for the most critically ill PAH patients already on optimized conventional treatment.
