Unmet Need
COVID-19 is characterized by vascular inflammation and thrombosis, including elevations in P-selectin, a mediator of inflammation released by endothelial cells. Patients with serious infection are more likely to have COVID-19 associated coagulopathy than patients with mild infection, and those who die from COVID-19 are more likely to have met the coagulopathy criteria. Thus, hospitalized COVID-19 patients in U.S. are given anticoagulants, mainly heparins, for prophylaxis or treatment. However, no specific antithrombotic treatment has shown to be promising in decreasing in-hospital mortality so far. Hence, novel strategies to treat coagulopathy in COVID-19 patients are urgently needed.
Technology Overview
The invention describes a method to use an inhibitor of P-selectin to treat COVID-19 patients with coagulopathy. The inventor proposed that COVID-19 causes endothelial injury, leading to microvascular inflammation and microvascular thrombosis in COVID-19 patients. As P-selectin mediates the initial rolling of leukocytes onto the inflamed endothelium and activates monocytes to synthesize tissue factor, an essential cofactor in the initiation of the extrinsic pathway of blood coagulation, the inventor proposed that a P-selectin inhibitor will decrease vascular inflammation and vascular thrombosis in COVID-19 patients and improve their treatment outcomes. Several recent publications on COVID-19 associated coagulopathy have supported P-selectin as a potential therapeutic target.
Stage of Development
The inventor has completed a clinical trial with Novartis (NCT04435184) to test crizanlizumab’s safety and efficacy in improving outcomes of COVID-19 patients.
We tested the effect of P-selectin inhibition on biomarkers of thrombosis and inflammation in patients with COVID-19. Hospitalized patients with moderate COVID-19 were randomly assigned to receive either placebo or crizanlizumab, a P-selectin inhibitor, in a double-blind fashion. Crizanlizumab reduced P-selectin levels by 89%. Crizanlizumab increased D-dimer levels by 77% and decreased prothrombin fragment. There were no significant differences between crizanlizumab and placebo for clinical endpoints. Crizanlizumab was well tolerated. Crizanlizumab may induce thrombolysis in the setting of COVID-19. (Crizanlizumab for Treating COVID-19 Vasculopathy
Publication
Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial - ScienceDirect
