Sotatercept: potential new treatment option for PAH

Sotatercept improved right ventricular-pulmonary arterial (RV-PA) coupling and RV function in patients with pulmonary arterial hypertension (PAH). This was shown by new cardiac and pulmonary function data from the ongoing phase 2 PULSAR trial of sotatercept [1]. This abstract won the AHA’s “Cardiopulmonary Best Abstract” award.

Sotatercept is a novel investigatory agent designed to be a selective ligand trap for members of the transforming growth factor (TGF)-β superfamily to reset signalling cascades that drive PAH. PULSAR (NCT03496207) is an ongoing, double-blind, placebo-controlled study in which PAH patients (mean age 48 years) were randomised in a 3:3:4 ratio to receive placebo, sotatercept 0.3 mg/kg, or sotatercept 0.7 mg/kg subcutaneously every 21 days over a 24-week treatment period, in combination with stable background PAH standard-of-care therapies. The primary endpoint is the change from baseline in pulmonary vascular resistance (PVR) over 24 weeks. The key secondary endpoint is 6-minute walk distance (6MWD). Following the 24 weeks, double-blind treatment period, participants were able to roll over to an 18-month extension period.

The top-line results of PULSAR were reported at the recent American Thoracic Society (ATS) meeting. They showed a 34% overall reduction of PVR (P=0.0027 for the 0.3 mg/kg sotatercept group; P<0.001 for the 0.7 mg/kg sotatercept group), as well as significantly improved 6MWD results after 24 weeks [2]. At the AHA Scientific Sessions, Prof. Vallerie McLaughlin (University of Michigan, USA) presented echocardiography data from the first 94 of 106 patients enrolled in the trial. The RV end-diastolic area was reduced significantly in both the 0.3 and 0.7 mg/kg sotatercept groups (P=0.0122 and P<0.001, respectively), as was the RV end-systolic area (P=0.0043 and P<0.001). Accordingly, RV fractional area change improved but only significantly in the higher dose group (P=0.0598 and P=0.0078). Pulmonary artery systolic pressure was reduced in both treatment arms (both P<0.001). For RV-PA coupling measured in 51 patients treated with sotatercept, improvements were significant (P=0.0015 and P=0.0198, respectively). Sotatercept was generally well-tolerated. 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 remodelling. Taken together with previously reported results of sotatercept’s haemodynamic and functional improvements, these outcomes suggest that sotatercept has the potential to become a paradigm-shifting new treatment option for patients with PAH.”

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   1. McLaughlin VV, et al. Sotatercept Improves Right Ventricular - Pulmonary Arterial Coupling and Right Ventricular Function in the Pulsar Study. Abstract 287, AHA Scientific Sessions 2020, 13–17 Nov.
   2. Badesch D, et al. Abstract B12, ATS Virtual 2020, 24 June.

 



Posted on 18 February 202113 June 2024