Using Sotatercept to Manage Pulmonary Arterial Hypertension
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on November 21st, 2025
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Pulmonary arterial hypertension (PAH) is characterized by the narrowing of pulmonary blood vessels, which limits blood flow to the lungs and impairs gas exchange. Current treatment options offer only partial benefit and do not fully halt disease progression, morbidity, or mortality. Supported by Merck, a recent study investigated the potential of sotatercept as a novel therapy for managing PAH.
The phase 3 clinical trial enrolled 320 participants with a mean age of 56 years, all diagnosed with World Health Organization Group 1 PAH. Using the REVEAL Lite 2 risk score-which estimates 1-year mortality risk based on parameters such as blood pressure, heart rate, renal function, 6-minute walk distance, and NT-proBNP levels-the study found that 28% of participants were at high risk (score >8), 51% were at intermediate risk (score 5–6), and the remainder were at low risk (score <5). At baseline, the cohort had an NT-proBNP level of approximately 956 pg/mL, an estimated glomerular filtration rate (eGFR) of 83.4 mL/min, and a pulmonary vascular resistance (PVR) of 916 dyn·s·cm⁻⁵.
Participants were randomly assigned to receive either a placebo or subcutaneous sotatercept every 21 days, starting at 0.3 mg/kg and escalating to a target dose of 0.7 mg/kg. Sotatercept works by inhibiting activin signaling, thereby reducing the abnormal proliferation of vascular endothelial cells and preserving vessel lumen size.
After 13 months of follow-up, treatment with sotatercept reduced the risk of disease progression or clinical worsening by 76%. Patients receiving sotatercept also showed fewer declines in physical performance and a lower rate of hospitalization compared to those on placebo. The main adverse effects reported were epistaxis and telangiectasia, occurring more frequently in the sotatercept group. Future research should compare sotatercept directly with existing PAH therapies and include quality-of-life assessments to better evaluate its long-term clinical value.
The phase 3 clinical trial enrolled 320 participants with a mean age of 56 years, all diagnosed with World Health Organization Group 1 PAH. Using the REVEAL Lite 2 risk score-which estimates 1-year mortality risk based on parameters such as blood pressure, heart rate, renal function, 6-minute walk distance, and NT-proBNP levels-the study found that 28% of participants were at high risk (score >8), 51% were at intermediate risk (score 5–6), and the remainder were at low risk (score <5). At baseline, the cohort had an NT-proBNP level of approximately 956 pg/mL, an estimated glomerular filtration rate (eGFR) of 83.4 mL/min, and a pulmonary vascular resistance (PVR) of 916 dyn·s·cm⁻⁵.
Participants were randomly assigned to receive either a placebo or subcutaneous sotatercept every 21 days, starting at 0.3 mg/kg and escalating to a target dose of 0.7 mg/kg. Sotatercept works by inhibiting activin signaling, thereby reducing the abnormal proliferation of vascular endothelial cells and preserving vessel lumen size.
After 13 months of follow-up, treatment with sotatercept reduced the risk of disease progression or clinical worsening by 76%. Patients receiving sotatercept also showed fewer declines in physical performance and a lower rate of hospitalization compared to those on placebo. The main adverse effects reported were epistaxis and telangiectasia, occurring more frequently in the sotatercept group. Future research should compare sotatercept directly with existing PAH therapies and include quality-of-life assessments to better evaluate its long-term clinical value.