Published: 1 April 2021
Authors: Marc Humbert, M.D., Ph.D., Vallerie McLaughlin, M.D., J. Simon R. Gibbs, M.D., Mardi Gomberg-Maitland, M.D., Marius M. Hoeper, M.D., Ioana R. Preston, M.D., Rogerio Souza, M.D., Ph.D., Aaron Waxman, M.D., Ph.D., Pilar Escribano Subias, M.D., Ph.D., Jeremy Feldman, M.D., Gisela Meyer, M.D., David Montani, M.D., Ph.D., et al., for the PULSAR Trial Investigators
Source: This abstract has been sourced from NZ Respiratory Research Review Issue 190
Pulmonary arterial hypertension is characterized by pulmonary vascular remodeling, cellular proliferation, and poor long-term outcomes. Dysfunctional bone morphogenetic protein pathway signaling is associated with both hereditary and idiopathic subtypes. Sotatercept, a novel fusion protein, binds activins and growth differentiation factors in the attempt to restore balance between growth-promoting and growth-inhibiting signaling pathways.
In this 24-week multicenter trial, we randomly assigned 106 adults who were receiving background therapy for pulmonary arterial hypertension to receive subcutaneous sotatercept at a dose of 0.3 mg per kilogram of body weight every 3 weeks or 0.7 mg per kilogram every 3 weeks or placebo. The primary end point was the change from baseline to week 24 in pulmonary vascular resistance.
Baseline characteristics were similar among the three groups. The least-squares mean difference between the sotatercept 0.3-mg group and the placebo group in the change from baseline to week 24 in pulmonary vascular resistance was −145.8 dyn·sec·cm−5 (95% confidence interval [CI], −241.0 to −50.6; P=0.003). The least-squares mean difference between the sotatercept 0.7-mg group and the placebo group was −239.5 dyn·sec·cm−5 (95% CI, −329.3 to −149.7; P<0.001). At 24 weeks, the least-squares mean difference between the sotatercept 0.3-mg group and the placebo group in the change from baseline in 6-minute walk distance was 29.4 m (95% CI, 3.8 to 55.0). The least-squares mean difference between the sotatercept 0.7-mg group and the placebo group was 21.4 m (95% CI, −2.8 to 45.7). Sotatercept was also associated with a decrease in N-terminal pro–B-type natriuretic peptide levels. Thrombocytopenia and an increased hemoglobin level were the most common hematologic adverse events. One patient in the sotatercept 0.7-mg group died from cardiac arrest.
Treatment with sotatercept resulted in a reduction in pulmonary vascular resistance in patients receiving background therapy for pulmonary arterial hypertension. (Funded by Acceleron Pharma; PULSAR ClinicalTrials.gov number, NCT03496207. opens in new tab.)
Link to full article
NZ Respiratory Research Review Issue 183