Sotatercept: A novel therapeutic approach for pulmonary arterial hypertension through transforming growth factor-β signaling modulation.

Abstract

Pulmonary arterial hypertension (PAH) is a progressive disease marked by degeneration of the lung's blood vessels. As the disease progresses, the resistance to blood flow in the pulmonary arteries increases, putting a strain on the right side of the heart as it pumps blood through the lungs. PAH is characterized by changes in the structure of blood vessels and excessive cell growth. Untreated PAH leads to irreversible right-sided heart failure, often despite medical intervention. Patients experience a gradual decline in function until they are unable to perform daily activities. Advances in treatment have improved the prognosis for many PAH patients. Currently approved therapies target the prostacyclin, endothelin, nitric oxide, or phosphodiesterase pathways to slow the progression of the disease. To address the unmet need for effective PAH therapies, research efforts are focused on identifying new targets and developing therapies that specifically address the underlying disease mechanisms and restore vascular wall homeostasis. Among these, sotatercept, a fusion protein that targets the transforming growth factor-β superfamily signaling pathway, has emerged as a promising therapeutic option. In this review, we examine the available evidence from clinical trials to assess the potential of sotatercept as a treatment for PAH.