Omeros Corporation reports recovery and survival of all patients in a study evaluating narsoplimab with acute respiratory distress syndrome associated with COVID-19.

Omeros Corporation reported the results of a compassionate-use study evaluating narsoplimab, Omeros’ investigational human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2) in the treatment of COVID-19 patients with Acute Respiratory Distress Syndrome (ARDS), a severe and life-threatening symptom of COVID-19. All patients initially required mechanical ventilation, and all recovered and survived with narsoplimab treatment. A manuscript detailing the results of the study has been accepted for publication in the peer-reviewed journal Immunobiology. A pre-publication copy of the manuscript can be accessed at https://www.sciencedirect.com/science/article/pii/S0171298520304459. Study Origin : The study was initiated in response to a request from treating physicians at the Papa Giovanni XXIII Hospital in Bergamo, Italy. The principal investigator, Alessandro Rambaldi, MD, Professor of Hematology at the University of Milan and Head of the Department of Hematology and Oncology at Papa Giovanni, was a lead investigator in the pivotal trial for narsoplimab in HSCT-TMA. Given the clinical and pathologic similarities between COVID-19 and HSCT-TMA, Professor Rambaldi requested that narsoplimab be made available under compassionate use for patients at his hospital in Bergamo, the initial epicenter of the COVID-19 pandemic in Europe. “The patients that we treated with narsoplimab were critically ill, and the uniformly successful outcomes were truly impressive,” said Professor Rambaldi. “Also of importance in this terribly sick population studied, the drug was well tolerated, showing no adverse effects. The pathophysiology of COVID-19 appears to be consistent with that of stem cell transplant-associated TMA, and the mechanism of the lectin pathway inhibitor narsoplimab looks to be well suited to treat the often-lethal manifestations of both disorders. The outcomes in these six patients provide further evidence of the potential role of narsoplimab in treating diseases caused by endothelial damage.” Study Results :In this study, the first time a lectin-pathway inhibitor was used to treat COVID-19, six COVID-19 patients with ARDS requiring continuous positive airway pressure (CPAP) or intubation received narsoplimab. The median age of the patients was 57 years (range 47 – 63 years), 83 percent were men, and all had comorbidities. At baseline, circulating endothelial cell (CEC) counts and serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer and aspartate aminotransferase (AST) – all markers of endothelial/cellular damage and/or inflammation – were significantly elevated. Narsoplimab treatment was begun within 48 hours of initiation of mechanical ventilation. Dosing occurred twice weekly for two to four weeks.All narsoplimab-treated patients recovered, survived and were discharged from the hospital Narsoplimab treatment was associated with rapid and sustained reduction across all assessed markers of endothelial/cellular damage and/or inflammation – CEC, IL-6, IL-8, CRP, LDH, D-dimer and AST Temporal patterns of laboratory markers were consistent with the observed clinical improvement In particular, CEC counts appear to be a reliable tool to evaluate endothelial damage and treatment response in this disease. The temporal improvement of IL-6 and IL-8 with narsoplimab treatment suggests that lectin pathway activation may precede cytokine elevation in COVID-19 and that lectin pathway inhibition has a beneficial effect on the cytokine storm described in patients with COVID-19 infection.The courses of two patients (one requiring intubation and the other on CPAP) were further complicated by massive bilateral pulmonary thromboses, and both patients recovered with narsoplimab, possibly benefitting from the drug’s anticoagulant effects. Narsoplimab was well tolerated in the study and no adverse drug reactions were reported. Two control groups with similar entry criteria and baseline characteristics were used for retrospective comparison, both showing substantial mortality rates at 32 percent and 53 percent.