Reduction in D-dimer levels after treatment with Auxora in patients with severe COVID-19 pneumonia

A phase 2 double-blinded trial (CARDEA) ( NCT04345614 ) in patients diagnosed with COVID-19 revealed that intravenous zegocractin treatment (Auxora™) was associated with improved clinical outcomes compared to standard of care (SOC). D-dimer serum levels is a biomarker of thrombosis in COVID-19, and elevated levels are directly correlated with a high risk of poor outcomes. Here, we report biomarker analyses from blood samples collected from patients in that study. Quantification of D-dimer levels was the primary endpoint, and secondary endpoints measured levels of angiopoietin 1 (Ang1), angiopoietin 2 (Ang2), soluble CD25 (sCD25), and renin. CARDEA was conducted in 17 U.S. clinical centers. Patients were randomly assigned to receive Auxora plus SOC (n=143) or placebo plus SOC (n=141). The medications were administered by a 4-h intravenous infusion at 2.0 mg/kg (1.25 mL/kg) at 0-h and 1.6 mg/kg (1 mL/kg) at 24 h and 48 h. Patients in the Auxora group had a baseline mean D-dimer value of 2.61 mg/L and those in the placebo group had a value of 2.05 mg/L. Treatment with Auxora resulted in a statistically significant decrease in D-dimer levels within the first 72 h compared to placebo (delta= -0.92; [95% CI: -1.82, -0.02]; p <0.046). The decrease in D-dimer levels correlated with an increase in imputed PaO 2 /FiO 2 at 72 h (r: -0.193; p <0.05) and improved clinical status at 168 h (r: 0.218, p <0.01). Auxora treatment reduced levels of Ang2 and sCD25, and increased Ang1 levels compared to placebo. Auxora treatment significantly reduced D-dimer levels in patients diagnosed with COVID-19, and the decrease was associated with an improved clinical status. • Inhibition of calcium release-activated calcium channels with Auxora, a novel Orai1 inhibitor, in patients with severe COVID-19 was associated with improved outcomes. • Treatment with Auxora was associated with a decrease in D-Dimer levels over 72 hours. • Treatment with Auxora was associated with biomarker changes that suggested endothelial stabilization. • Further studies investigating the effect of Auxora on endothelial dysfunction in patients with acute kidney injury and ARDS will be conducted