Sotatercept shows improvement in hemodynamics, exercise capacity in patients with PAH

In a preliminary analysis of the ongoing SPECTRA study, patients with pulmonary arterial hypertension treated with sotatercept had improvements in hemodynamics, exercise capacity and 6-minute walk distance.

At the American Thoracic Society International Conference, Aaron B. Waxman, MD, PhD, director of the Pulmonary Vascular Disease Program at Brigham and Women’s Hospital, presented interim results of the phase 2a, single-arm, open-label, exploratory SPECTRA study, which assessed the effects of sotatercept (Acceleron Pharma) in patients with PAH.

Sotatercept is a first-in-class therapeutic fusion protein targeting an imbalance between growth-promoting and growth-inhibiting signaling pathways. Healio previously reported results that demonstrated sotatercept for 24 weeks resulted in a reduction in pulmonary vascular resistance.

Waxman presented an interim look at this study, focusing on peak exercise results in 10 patients (mean age, 45 years; 60% women) who completed 24-week assessments. All patients had WHO Group 1 PAH, were in WHO functional class III, had right heart catheterization with PVR 4 Wood units, baseline 6-minute walk distance of 100 m to 550 m, and were on stable combination PAH therapy. All patients received sotatercept at 3-week intervals and underwent right heart catheterization and invasive cardiopulmonary exercise tests at baseline and 6 months.

The primary endpoint was change from baseline to 24 weeks in peak oxygen uptake. Secondary endpoints were change from baseline to 24 weeks in 6-minute walk distance and change from baseline to 24 weeks in exercise capacity measures, including ventilation/carbon dioxide production slope, arteriovenous oxygen content difference, workload and peak hemodynamics.

Results showed a more than 30% improvement in supine resting hemodynamics, including pulmonary vascular resistance (from 576.4 dynes/seconds/cm⁵ at baseline to 369.2 dynes/seconds/cm⁵ at 24 weeks) and mean pulmonary artery pressure (from 43.4 mm Hg to 30.6 mm Hg).

In addition, researchers observed improvements in peak exercise measures, including peak oxygen uptake (from 12.7 mL/min/kg at baseline to 14 mL/min/kg at 24 weeks), ventilatory efficiency (from 50.7 to 41.2), total workload (from 72.3 W to 88.5 W) and arteriovenous oxygen content difference (from 9.7 L/min to 11.5 L/min).

Data were available for 6-minute walk distance for nine patients. In these patients, 6-minute walk distance improved by an average of 72.4 m from baseline to 24 weeks.

Seventy-six percent of patients reported treatment-emergent adverse events as of the interim data cut, with a median follow-up of 5.5 months. There were three serious treatment-emergent adverse events, including hematochezia, complication associated with central line and fluid overload; however, no serious adverse events were related to sotatercept treatment, Waxman said.

“In this preliminary analysis of patients in the ongoing SPECTRA study, we saw encouraging results in resting hemodynamics, exercise performance based on invasive cardiopulmonary exercise test, and 6-minute walk distance,” Waxman said. “Safety findings were consistent with previous reports in PAH and in other patient populations.”

Reference:

Waxman AB, et al. Am J Respir Crit Care Med. 2021;doi:10.1164/ajrccm-conference.2021.