PULSAR open-label extension: interim results from a phase 2 study of the efficacy and safety of sotatercept when added to standard of care for the treatment of pulmonary arterial hypertension (PAH)

Abstract

<b>Background:</b> New therapies are needed to target vascular remodeling in PAH. Sotatercept is a novel first-in-class fusion protein that acts by rebalancing deficient BMPR2 signaling. <b>Aims and Objectives:</b> To determine the safety and efficacy of sotatercept for the treatment of PAH. <b>Methods:</b> 106 WHO Group 1 PAH patients (pts) were enrolled: WHO functional class (FC)II-III; baseline pulmonary vascular resistance&nbsp;of ≥5 Wood units; 6MWD of 150-550m. Sotatercept (0.3mg/kg or 0.7mg/kg)&nbsp;was added to standard of care (SOC) for a 24-week (wk) double-blind, placebo-controlled treatment period. The extension&nbsp;period is ongoing&nbsp;in which&nbsp;sotatercept-treated pts maintain&nbsp;their&nbsp;current&nbsp;dose level, and placebo-treated pts&nbsp;were&nbsp;re-randomized to&nbsp;0.3mg/kg or 0.7mg/kg&nbsp;sotatercept. <b>Results:</b> Continuation of sotatercept treatment for up to 48 wks maintained the improvements observed in 6MWD, NT-proBNP, and change in WHO FC at 24 weeks versus baseline. Pts re-randomized from placebo to sotatercept showed improvements in 6MWD, NT-proBNP, and change in WHO FC at 48 wks compared to 24 wks and baseline. Cumulatively during the trial, 30/106(28.3%) patients reported serious treatment-emergent adverse events (TEAEs), 9(8.5%) TEAEs led to study discontinuation, and 2(1.9%) TEAEs led to death. <b>Conclusions:</b> Continued sotatercept treatment maintained clinical efficacy across multiple study endpoints for up to 48 wks. Importantly, placebo assignment did not affect the ability to respond after 24 wks. Safety was consistent with previous reports in PAH and other pt populations.