Pericardial effusion in sotatercept phase 3 trials: insights from STELLAR and ZENITH
Marius M. Hoeper, Ioana R. Preston, Mardi Gomberg‐Maitland, Aaron B. Waxman, Yaru Shi, Jianxin Lin, Harald S. Mackenzie, María José Loureiro, Vallerie V. McLaughlin, Marc Humbert, for the STELLAR and ZENITH trial investigators
Abstract
<title>Extract</title> Pulmonary arterial hypertension (PAH) is associated with significant morbidity and mortality. The presence of pericardial effusion is associated with an increased mortality risk in patients with PAH, with the highest mortality rates occurring in patients with more severe pericardial effusion. [1–5] The prevalence of pericardial effusion on echocardiography reported in previous studies in PAH patients was generally around 30%, predominantly trace or small. [1] Few placebo-controlled clinical trials have reported on the occurrence of pericardial effusion in patients with PAH. However, a recent US Securities and Exchange Commission filing indicated that a clinical trial program investigating cibotercept, an activin receptor type IIB ligand trap, was unexpectedly halted due to the occurrence of pericardial effusions in trial participants. Pericardial effusion was the most frequently occurring adverse event (AE), occurring within 24 weeks after treatment initiation and reported in 25% to 40% of the participants assigned to different doses of cibotercept, with evidence of dose-dependence by frequency of occurrence and severity, compared with 10% in the placebo group. [6] These findings raise the question of whether treatment with other activin signalling inhibitors might also be associated with an increased risk of pericardial effusion.