On Aug. 10, 2020, Omeros reported the results of a compassionate-use study evaluating narsoplimab, Omerosﾒ 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. All patients initially required mechanical ventilation, and all recovered and survived with narsoplimab treatment. A manuscript detailing the results of the study was accepted for publication in the peer-reviewed journal Immunobiology.

In COVID-19, ARDS and thrombotic events are frequent, life-threatening complications. Autopsies commonly show arterial thrombosis and severe endothelial damage. Endothelial damage, which can play an early and central pathogenic role in ARDS and thrombosis, activates the lectin pathway of complement. MASP-2, the lectin pathway’s effector enzyme and the target for narsoplimab, binds the nucleocapsid protein of severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) – the virus responsible for COVID-19 – resulting in complement activation and lung injury. Numerous articles have been published detailing and further confirming specific aspects of the central role of endothelial injury, activation of the complement system and the lectin pathway and thrombosis development in COVID-19.

Narsoplimab also has been evaluated in patients in hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), another often-lethal thrombotic disorder associated with endothelial damage. In its pivotal HSCT-TMA trial, narsoplimab-treated patients demonstrated marked improvement in laboratory and clinical endpoints and unexpected survival. With FDA’s Breakthrough Therapy designation, submission of a rolling Biologics Licensing Application for narsoplimab is underway in this indication.

In addition to its inhibitory effect on lectin pathway activation, narsoplimab has been shown to block microvascular injury-associated thrombus formation as well as MASP-2-mediated activation of thrombin, kallikrein and factor XII. These unique anticoagulant effects may provide therapeutic benefits in both HSCT-TMA and COVID-19. Importantly, narsoplimab leaves the complement system’s classical pathway and adaptive immune response fully intact, and does not appear to increase infection risk.

Omeros has completed a pivotal trial of narsoplimab in hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) and submission of a rolling Biologics License Application is underway. Phase 3 clinical programs are also in progress for narsoplimab in immunoglobulin A (IgA) nephropathy, and in atypical hemolytic uremic syndrome (aHUS). The FDA has granted narsoplimab breakthrough therapy designations for HSCT-TMA and for IgA nephropathy; orphan drug status for the prevention (inhibition) of complement-mediated thrombotic microangiopathies, for the treatment of HSCT-TMA and for the treatment of IgA nephropathy; and fast track designation for the treatment of patients with aHUS. The European Medicines Agency has granted orphan drug designation to narsoplimab for treatment in HSCT and for treatment of primary IgA nephropathy.