Despite the many causes of Acute Respiratory Distress Syndrome (ARDS) a breach of the microvascular barrier that separates blood cells from airspace is an early shared event. The resulting inflammatory infiltrate and lung edema drastically reduces gas exchange leading to multiorgan failure and death. While improvements in supportive care and ventilator management have reduced mortality over the last several decades in patients with ARDS, no effective pharmacological treatments for the prevention of ARDS in patients at risk or as treatment for ARDS due to any cause have been developed.
COVID-19 is a rapidly progressive respiratory tract infection that quickly leads to respiratory failure, mortality, and overwhelmed healthcare systems (intensive care units [ICU] and ventilatory capacity). Approximately 14% of people with COVID-19 develop severe disease that requires hospitalization and oxygen support and 5% require admission to the ICU (NCPERE, 2020). In addition to respiratory disease, cardiovascular complications are emerging as important factors in COVID-19 outcomes, potentially due to endothelial cell dysfunction (Varga et al., 2020) and abnormal coagulation (i.e., disseminated intravascular coagulation [DIC]) (Tang et al., 2020; Zhou et al., 2020). In patients with COVID-19, endothelial cell involvement has been shown across vascular beds of various organs including kidney, heart, small intestine, liver, and lung, with evidence of direct viral infection of the endothelial cell and diffuse endothelial inflammation (Varga et al., 2020). An effective host-targeted intervention to treat and reduce progression of pulmonary and vascular pathology in COVID-19 is urgently needed.
Razuprotafib represents a potentially unique, first-in-class, host-targeted therapy for ARDS and COVID-19. Razuprotafib restores Tie2 activation to stabilize the vasculature which may provide breakthrough potential for reducing the severity of COVID-19 associated pulmonary and vascular pathology resulting in more rapid recovery, fewer patients requiring mechanical ventilation, decreased time in ICU on ventilator support, and concomitant reduction in morbidity and mortality. Additionally, razuprotafib together with emerging antiviral drugs could provide the optimal combination of host and virus targeted therapy for prevention and treatment of COVID‑19 and COVID-19 related ARDS. Considering the centrality of pulmonary and vascular pathology to coronavirus morbidity and mortality, a plan has been developed to test the efficacy of subcutaneous (SC) administration of razuprotafib in patients with COVID-19.
Two phase 2 clinicals trials, I-SPY COVID-19 and RESCUE, are slated to begin recruiting patients in Q3/4 2020 in patients with critical and moderate to severe COVID-19, respectively.