{"id":273,"date":"2023-09-06T17:42:48","date_gmt":"2023-09-06T17:42:48","guid":{"rendered":"https:\/\/www.merckconnect.com\/winrevair\/?page_id=273"},"modified":"2026-04-02T07:51:51","modified_gmt":"2026-04-02T07:51:51","slug":"mechanism-of-action","status":"publish","type":"page","link":"https:\/\/www.merckconnect.com\/winrevair\/mechanism-of-action\/","title":{"rendered":"Mechanism of Action"},"content":{"rendered":"\n\n
<\/div>\n\n\n\n
\n
<\/div>\n\n\n\n
\n\n

WINREVAIRTM<\/sup> (sotatercept-csrk) targets a key driver of PAH\u2014imbalanced proliferative signaling\u2014through activin signaling inhibition1,2<\/sup><\/strong><\/h1><\/div>\n\n\n\n
<\/div>\n\n\n\n
<\/div>\n\n\n
The image is divided into 3 columns. Column 1 (far left) illustrates how imbalanced signaling in PAH is caused by increased levels of Activin A which bind to ActRIIA, resulting in an increase in pro-proliferative ActRIIA signaling and a decrease in anti-proliferative BMPRII signaling. The imbalance of ActRIIA-BMPRII signaling underlying PAH results in pulmonary vascular hyperproliferation. Column 2 (middle) illustrates how, based on preclinical studies, WINREVAIR improves the balance in signaling by binding to excess Activin A. Column 3 (far right) illustrates how, based on preclinical studies, modulating pulmonary vascular hyperproliferation with WINREVAIR may lead to thinner vessel walls, partial reversal of right ventricular remodeling, and improved hemodynamics.<\/desc><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/defs><\/rect><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/svg> <\/div><\/div>
The image is divided into 3 columns. Column 1 (far left) illustrates how imbalanced signaling in PAH is caused by increased levels of Activin A which bind to ActRIIA, resulting in an increase in pro-proliferative ActRIIA signaling and a decrease in anti-proliferative BMPRII signaling. The imbalance of ActRIIA-BMPRII signaling underlying PAH results in pulmonary vascular hyperproliferation. Column 2 (middle) illustrates how, based on preclinical studies, WINREVAIR improves the balance in signaling by binding to excess Activin A. Column 3 (far right) illustrates how, based on preclinical studies, modulating pulmonary vascular hyperproliferation with WINREVAIR may lead to thinner vessel walls, partial reversal of right ventricular remodeling, and improved hemodynamics.<\/desc><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/defs><\/rect><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/svg> <\/div><\/div>
The image is divided into 3 columns. Column 1 (far left) illustrates how imbalanced signaling in PAH is caused by increased levels of Activin A which bind to ActRIIA, resulting in an increase in pro-proliferative ActRIIA signaling and a decrease in anti-proliferative BMPRII signaling. The imbalance of ActRIIA-BMPRII signaling underlying PAH results in pulmonary vascular hyperproliferation. Column 2 (middle) illustrates how, based on preclinical studies, WINREVAIR improves the balance in signaling by binding to excess Activin A. Column 3 (far right) illustrates how, based on preclinical studies, modulating pulmonary vascular hyperproliferation with WINREVAIR may lead to thinner vessel walls, partial reversal of right ventricular remodeling, and improved hemodynamics.<\/desc><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/g><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/mask><\/path><\/g><\/path><\/mask><\/path><\/g><\/path><\/mask><\/path><\/g><\/path><\/mask><\/path><\/mask><\/rect><\/g><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/use><\/pattern><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/image><\/defs><\/svg> <\/div><\/div><\/div>\n\n\n
<\/div>\n\n\n\n

WINREVAIR is the first and only PAH treatment to target the activin signaling pathway3<\/sup><\/h2><\/div>\n\n\n\n
<\/div>\n\n\n
This figure illustrates a cross-section of a pulmonary artery comparing a normal artery with one with PAH. The vessel wall layers are labeled as endothelial cells (inner layer), smooth muscle cells (middle layer), and adventitia (outer layer). The vessel wall of the PAH artery is thicker than the normal artery and the lumen is narrower.<\/desc><\/path><\/mask><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/g><\/use><\/pattern><\/feFlood><\/feColorMatrix><\/feOffset><\/feGaussianBlur><\/feColorMatrix><\/feBlend><\/feBlend><\/filter><\/feFlood><\/feColorMatrix><\/feOffset><\/feGaussianBlur><\/feColorMatrix><\/feBlend><\/feBlend><\/filter><\/rect><\/clipPath><\/image><\/defs><\/svg> <\/div><\/div>
This figure illustrates a cross-section of a pulmonary artery comparing a normal artery with one with PAH. The vessel wall layers are labeled as endothelial cells (inner layer), smooth muscle cells (middle layer), and adventitia (outer layer). The vessel wall of the PAH artery is thicker than the normal artery and the lumen is narrower.<\/desc><\/path><\/mask><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/g><\/use><\/pattern><\/feFlood><\/feColorMatrix><\/feOffset><\/feGaussianBlur><\/feColorMatrix><\/feBlend><\/feBlend><\/filter><\/feFlood><\/feColorMatrix><\/feOffset><\/feGaussianBlur><\/feColorMatrix><\/feBlend><\/feBlend><\/filter><\/rect><\/clipPath><\/image><\/defs><\/svg> <\/div><\/div>
This figure illustrates a cross-section of a pulmonary artery comparing a normal artery with one with PAH. The vessel wall layers are labeled as endothelial cells (inner layer), smooth muscle cells (middle layer), and adventitia (outer layer). The vessel wall of the PAH artery is thicker than the normal artery and the lumen is narrower.<\/desc><\/path><\/mask><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/g><\/use><\/pattern><\/feFlood><\/feColorMatrix><\/feOffset><\/feGaussianBlur><\/feColorMatrix><\/feBlend><\/feBlend><\/filter><\/feFlood><\/feColorMatrix><\/feOffset><\/feGaussianBlur><\/feComposite><\/feColorMatrix><\/feBlend><\/feBlend><\/filter><\/rect><\/clipPath><\/image><\/defs><\/svg> <\/div><\/div><\/div>\n\n
This figure describes PAH therapeutic targets and is organized into two domains: \u201cPulmonary vascular proliferation\u201d on the left and \u201cPulmonary vascular tone\u201d on the right. The left domain is associated with WINREVAIR and highlights its role as an activin signaling inhibitor acting on the activin signaling pathway. The stated primary effect is anti-proliferation. Within the \u201cPulmonary vascular tone\u201d domain, three classes of therapies are shown: (1) endothelin receptor antagonists acting on the endothelin pathway; (2) phosphodiesterase type 5 inhibitors (PDE5is) and soluble guanylate cyclase (sGC) stimulators acting on the NO-sGC\u2013cGMP pathway; and (3) prostacyclin derivatives acting on the prostacyclin pathway. The primary effect of these classes is vasodilation.<\/desc><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/rect><\/clipPath><\/defs><\/svg> <\/div><\/div>
This figure describes PAH therapeutic targets and is organized into two domains: \u201cPulmonary vascular proliferation\u201d on the left and \u201cPulmonary vascular tone\u201d on the right. The left domain is associated with WINREVAIR and highlights its role as an activin signaling inhibitor acting on the activin signaling pathway. The stated primary effect is anti-proliferation. Within the \u201cPulmonary vascular tone\u201d domain, three classes of therapies are shown: (1) endothelin receptor antagonists acting on the endothelin pathway; (2) phosphodiesterase type 5 inhibitors (PDE5is) and soluble guanylate cyclase (sGC) stimulators acting on the NO-sGC\u2013cGMP pathway; and (3) prostacyclin derivatives acting on the prostacyclin pathway. The primary effect of these classes is vasodilation.<\/desc><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/rect><\/clipPath><\/defs><\/svg> <\/div><\/div>
<\/rect><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/path><\/g><\/svg> <\/div><\/div><\/div>\n\n\n
<\/div>\n\n\n\n
<\/div>\n\n\n\n

ActRIIA = activin receptor type IIA; BMP = bone morphogenetic protein; BMPRII = bone morphogenetic protein receptor type II; cGMP = cyclic guanosine monophosphate; NO = nitric oxide; PDE5i = phosphodiesterase 5 inhibitor; sGC = soluble guanylate cyclase.<\/p><\/div><\/div>\n\n\n\n

<\/div>\n\n\n\n\n
\"\"\/<\/picture><\/figure><\/div>

WINREVAIR targets a novel pathway involved in regulating proliferative signaling, which is thought to be a key driver of pulmonary vascular remodeling2<\/sup><\/h4><\/div><\/div><\/div>\n\n\n\n
<\/div>\n\n\n\n

References:<\/strong>
1. <\/strong>Hoeper MM, Badesch DB, Ghofrani HA, et al; STELLAR Trial Investigators. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med<\/em>. 2023;388(16):1478-1490. <\/p><\/div><\/div>\n\n\n\n

\u20282.<\/strong> Humbert M, McLaughlin V, Gibbs JSR, et al; PULSAR Trial Investigators. Sotatercept for the treatment of pulmonary arterial hypertension. N Engl J Med<\/em>. 2021;384(13):1204-1215. \u2028<\/p><\/div><\/div>\n\n\n\n

3.<\/strong> DailyMed database. Advanced search: “activin signaling inhibitor” in Mechanism of Action section. National Library of Medicine. Accessed October 20, 2025. htt\u200dp\u200ds:\/\/dailymed.nlm.nih\u200d.\u200dg\u200dov\/dailymed\/advanced-search.cfm <\/p><\/div><\/div>\n\n\n\n

4.<\/strong> Sahay S, Chakinala MM, Kim NH, et al. Contemporary treatment of pulmonary arterial hypertension: a US perspective. Am J Respir Crit Care Med<\/em>. 2024;210(5):581-592.<\/p><\/div><\/div>\n\n\n\n

<\/div>\n\n\n\n
<\/div>\n\n\n\n
\n
\n
Report exposure during pregnancy or lactation to the Merck Sharp & Dohme<\/span> LLC Adverse Event reporting line at 1-877-888-4231<\/span><\/strong><\/h6><\/div>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n
<\/div>\n<\/div>\n\n\n\n
<\/div>\n","protected":false},"excerpt":{"rendered":"

ActRIIA = activin receptor type IIA; BMP = bone morphogenetic protein; BMPRII = bone morphogenetic protein receptor type II; cGMP = cyclic…<\/p>\n","protected":false},"author":666,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"_trash_the_other_posts":false,"editor_notices":[],"footnotes":""},"ga4_page_audience":[911],"ga4_page_birn_id":[],"ga4_page_branding":[271],"ga4_page_businessunit":[278],"ga4_page_campaign":[],"ga4_page_content_purpose":[304],"ga4_page_customer_journey_stage":[338],"ga4_page_customer_specialty":[396],"ga4_page_experience":[],"ga4_page_indication":[507],"ga4_page_material_intent":[526],"ga4_page_product":[941],"ga4_page_region":[814],"ga4_page_therapeuticarea":[856],"user_role":[],"mhh-area-of-interest":[],"access":[],"user_status":[],"class_list":["post-273","page","type-page","status-publish"],"yoast_head":"\nMechanism of Action for WINREVAIR\u2122 (sotatercept-csrk)<\/title>\n<meta name=\"description\" content=\"Healthcare professionals can review the mechanism of action for WINREVAIR\u2122 (sotatercept-csrk).\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.merckconnect.com\/winrevair\/mechanism-of-action\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Mechanism of Action for WINREVAIR\u2122 (sotatercept-csrk)\" \/>\n<meta property=\"og:description\" content=\"Healthcare professionals can review the mechanism of action for WINREVAIR\u2122 (sotatercept-csrk).\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.merckconnect.com\/winrevair\/mechanism-of-action\/\" \/>\n<meta property=\"og:site_name\" content=\"Sotatercept\" \/>\n<meta property=\"article:modified_time\" content=\"2026-04-02T07:51:51+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.merckconnect.com\/winrevair\/wp-content\/uploads\/sites\/112\/2025\/07\/arrow_2.svg\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"2 minutes\" \/>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Mechanism of Action for WINREVAIR\u2122 (sotatercept-csrk)","description":"Healthcare professionals can review the mechanism of action for WINREVAIR\u2122 (sotatercept-csrk).","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.merckconnect.com\/winrevair\/mechanism-of-action\/","og_locale":"en_US","og_type":"article","og_title":"Mechanism of Action for WINREVAIR\u2122 (sotatercept-csrk)","og_description":"Healthcare professionals can review the mechanism of action for WINREVAIR\u2122 (sotatercept-csrk).","og_url":"https:\/\/www.merckconnect.com\/winrevair\/mechanism-of-action\/","og_site_name":"Sotatercept","article_modified_time":"2026-04-02T07:51:51+00:00","og_image":[{"url":"https:\/\/www.merckconnect.com\/winrevair\/wp-content\/uploads\/sites\/112\/2025\/07\/arrow_2.svg","type":"","width":"","height":""}],"twitter_card":"summary_large_image","twitter_misc":{"Est. reading time":"2 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/www.merckconnect.com\/winrevair\/mechanism-of-action\/","url":"https:\/\/www.merckconnect.com\/winrevair\/mechanism-of-action\/","name":"Mechanism of Action for WINREVAIR\u2122 (sotatercept-csrk)","isPartOf":{"@id":"https:\/\/www.merckconnect.com\/winrevair\/#website"},"primaryImageOfPage":{"@id":"https:\/\/www.merckconnect.com\/winrevair\/mechanism-of-action\/#primaryimage"},"image":{"@id":"https:\/\/www.merckconnect.com\/winrevair\/mechanism-of-action\/#primaryimage"},"thumbnailUrl":"https:\/\/www.merckconnect.com\/winrevair\/wp-content\/uploads\/sites\/112\/2025\/07\/arrow_2.svg","datePublished":"2023-09-06T17:42:48+00:00","dateModified":"2026-04-02T07:51:51+00:00","description":"Healthcare professionals can review the mechanism of action for WINREVAIR\u2122 (sotatercept-csrk).","breadcrumb":{"@id":"https:\/\/www.merckconnect.com\/winrevair\/mechanism-of-action\/#breadcrumb"},"inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.merckconnect.com\/winrevair\/mechanism-of-action\/"]}]},{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/www.merckconnect.com\/winrevair\/mechanism-of-action\/#primaryimage","url":"https:\/\/www.merckconnect.com\/winrevair\/wp-content\/uploads\/sites\/112\/2025\/07\/arrow_2.svg","contentUrl":"https:\/\/www.merckconnect.com\/winrevair\/wp-content\/uploads\/sites\/112\/2025\/07\/arrow_2.svg","width":90,"height":87},{"@type":"BreadcrumbList","@id":"https:\/\/www.merckconnect.com\/winrevair\/mechanism-of-action\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/www.merckconnect.com\/winrevair\/"},{"@type":"ListItem","position":2,"name":"Mechanism of Action"}]},{"@type":"WebSite","@id":"https:\/\/www.merckconnect.com\/winrevair\/#website","url":"https:\/\/www.merckconnect.com\/winrevair\/","name":"Sotatercept","description":"Just another vip-msd.com site","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.merckconnect.com\/winrevair\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-US"}]}},"acf":[],"_links":{"self":[{"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/pages\/273","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/users\/666"}],"replies":[{"embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/comments?post=273"}],"version-history":[{"count":189,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/pages\/273\/revisions"}],"predecessor-version":[{"id":7414,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/pages\/273\/revisions\/7414"}],"wp:attachment":[{"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/media?parent=273"}],"wp:term":[{"taxonomy":"ga4_page_audience","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/ga4_page_audience?post=273"},{"taxonomy":"ga4_page_birn_id","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/ga4_page_birn_id?post=273"},{"taxonomy":"ga4_page_branding","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/ga4_page_branding?post=273"},{"taxonomy":"ga4_page_businessunit","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/ga4_page_businessunit?post=273"},{"taxonomy":"ga4_page_campaign","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/ga4_page_campaign?post=273"},{"taxonomy":"ga4_page_content_purpose","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/ga4_page_content_purpose?post=273"},{"taxonomy":"ga4_page_customer_journey_stage","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/ga4_page_customer_journey_stage?post=273"},{"taxonomy":"ga4_page_customer_specialty","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/ga4_page_customer_specialty?post=273"},{"taxonomy":"ga4_page_experience","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/ga4_page_experience?post=273"},{"taxonomy":"ga4_page_indication","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/ga4_page_indication?post=273"},{"taxonomy":"ga4_page_material_intent","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/ga4_page_material_intent?post=273"},{"taxonomy":"ga4_page_product","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/ga4_page_product?post=273"},{"taxonomy":"ga4_page_region","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/ga4_page_region?post=273"},{"taxonomy":"ga4_page_therapeuticarea","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/ga4_page_therapeuticarea?post=273"},{"taxonomy":"user_role","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/user_role?post=273"},{"taxonomy":"mhh-area-of-interest","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/mhh-area-of-interest?post=273"},{"taxonomy":"access","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/access?post=273"},{"taxonomy":"user_status","embeddable":true,"href":"https:\/\/www.merckconnect.com\/winrevair\/wp-json\/wp\/v2\/user_status?post=273"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}