1. Treatment with sotatercept decreased pulmonary vascular resistance in patients with pulmonary arterial hypertension.
2. Sotatercept caused adverse side effects of thrombocytopenia and increased hemoglobin level.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Pulmonary arterial hypertension (PAH) is driven by reduced bone morphogenic protein receptor type 2 (BMP2) and increased activin signaling leading to weakened pulmonary endothelium. Sotatercept is a fusion protein that blocks activin signaling to restore the imbalance. This study evaluated the efficacy of sotatercept in patients with PAH who were receiving background therapy for the disease. The study found a significant decrease in pulmonary vascular resistance in patients treated with sotatercept compared to the control. Furthermore, patients receiving sotatercept also had improved six-minute walk distances. Thrombocytopenia and increased hemoglobin were commonly reported adverse events of sotatercept. Strengths of this study include its multicenter, double-blinded nature, and in-depth reporting on safety. However, weaknesses of the study included its small sample size and study duration, which limits the group’s ability to evaluate long-term efficacy and safety. Together, this study supports the continued investigation of sotatercept for PAH as the treatment demonstrated good safety and efficacy.
In-Depth [randomized controlled trial]: This phase II clinical trial evaluated the safety and efficacy of a chimeric protein named sotatercept for the treatment of pulmonary arterial hypertension. Patients who had class II or III pulmonary arterial hypertension as classified by the World Health Organization (WHO) were included in the study. Patients were excluded from the study if their PAH was associated with portopulmonary disease, schistosomiasis, and human immunodeficiency virus infection. From 43 centers, 106 patients were randomized in a 3:3:4 ratio for placebo, sotatercept at 0.3mg/kg body weight, and sotatercept at 0.7 mg/kg body weight, respectively. The primary endpoint was a change in the pulmonary vascular resistance after 24 weeks. The secondary endpoint was the improvement in 6-minute walk distance after 24 weeks. The study found a decrease of 162.2 dyn·sec·cm-5 in pulmonary vascular resistance in the 0.3mg group (least-squares mean difference, -145.8 dyn·sec·cm-5; 95% confidence interval [CI],-241.0 to -50.6; P=0.003) and 255.9 dyn·sec·cm-5 in the 0.7mg group (least-squares mean difference, -239.5 dyn·sec·cm-5; 95% CI,-329.3 to -149.7; P<0.001) when compared to the placebo group. As for the 6-minute walk distance, patients in the 0.3mg and 0.7mg group improved 58.1 and 50.1 meters, respectively, compared to the 28.7 meters in the placebo group. The study found serious adverse events in 26% of patients receiving 0.7mg/kg sotatercept with thrombocytopenia and hemoglobin increase being the most common when compared to 16% in the placebo group. Overall, the study determined the safety and efficacy profile for sotatercept in the treatment of PAH for patients with background therapy for the disease.
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