New cardiac and pulmonary function data from the ongoing phase 2 PULSAR trial of sotatercept in patients with pulmonary arterial hypertension (PAH) showed that sotatercept improved right ventricular-pulmonary arterial (RV-PA) coupling and RV function. This abstract won the American Heart Association’s “Cardiopulmonary Best Abstract” award.
Prof. Vallerie McLaughlin (University of Michigan, USA) presented echocardiography data from the first 94 patients enrolled in the phase 2 PULSAR trial (n=106) . PULSAR is a double-blind, placebo-controlled study in which PAH patients (mean age 48 years) were randomized in a 3:3:4 ratio to receive placebo, 0.3 mg/kg of sotatercept, or 0.7 mg/kg of sotatercept subcutaneously every 21 days in combination with stable background PAH standard-of-care therapies over a 24-week treatment period. Sotatercept is a novel investigational agent designed to be a selective ligand trap for members of the TGF-beta superfamily to reset signaling cascades that drive PAH. In patients with PAH, RV function deteriorates as a result of the pulmonary vascular remodeling that is a hallmark of the disease.
The primary endpoint of the trial is the change from baseline in pulmonary vascular resistance (PVR) over a 24-week treatment period. PVR, as measured by right heart catheterization, is the resistance that the heart must overcome to pump blood through the pulmonary circulatory system. The key secondary endpoint was 6-minute walk distance (6MWD). Following the 6-month, double-blind treatment period, participants were able to roll over to an 18-month extension period. As of 28 October 2020, 93 of 97 patients who participated in the 18-month extension period of the trial were still enrolled; 94 patients have now been treated with sotatercept for at least 12 months.
The topline results of PULSAR were reported at the recent American Thoracic Society, which showed a 34% reduction of PVR (for the 0.3 mg/kg sotatercept group P=0.0027; for the 0.7 mg/kg sotatercept group P<0.001), as well as significantly improved 6MWD results after 24 weeks of sotatercept .
Prof. McLaughlin focused her presentation on the echocardiography data from this trial. The RV end-diastolic area reduced significantly in both the 0.3 and 0.7 mg/kg sotatercept groups (P=0.0122 and P<0.001, respectively), as did the RV end-systolic area (P=0.0043 and P<0.001, respectively). Accordingly, RV fractional area change improved but only reached significance for the higher dose (P=0.0598 and P=0.0078, respectively). Pulmonary artery systolic pressure reduced in both treatment arms (both P<0.001). In the RV-PA coupling measured in 51 patients treated with sotatercept, improvements were significant (P=0.0015 and P=0.0198, respectively). Data analysis on the remaining patients is ongoing.
Sotatercept was generally well-tolerated in the trial. Adverse events observed in the study were generally consistent with previously published data on sotatercept in other diseases.
Prof. McLaughlin concluded: “The measurement of RV-PA coupling may offer important insights into how the RV is coping with increased pulmonary pressure. Although the assessment of RV-PA coupling non-invasively is a relatively new approach, these data are encouraging, as they demonstrate potential for RV remodeling. Taken together with previously reported results of sotatercept’s hemodynamic and functional improvements—as measured by reduced pulmonary vascular resistance and increased 6-minute walk distance—these outcomes suggest that sotatercept has the potential to become a paradigm-shifting new treatment option for patients with PAH.”
- McLaughlin V, et al. Sotatercept Improves Right Ventricular – Pulmonary Arterial Coupling and Right Ventricular Function in the Pulsar Study. Abstract 287, Virtual AHA Scientific Sessions 2020, 13-17 Nov.
- Badesch D, et al. Sotatercept for the treatment of pulmonary arterial hypertension. B12, ATS Virtual 2020, 24 June.