Research & Development
Omeros Touts Results of Study Evaluating Narsoplimab for Treatment of COVID-19-Associated Acute Respiratory Distress Syndrome
10 August 2020 - - US-based biopharmaceutical company Omeros Corp. (NASDAQ: OMER) has 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, 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, the company said.

Rationale for the use of narsoplimab for treatment of COVID-19 patients with ARDS
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.

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.

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 or intubation received narsoplimab.

The median age of the patients was 57 years (range 47 63 years), 83% were men, and all had comorbidities.

At baseline, circulating endothelial cell counts and serum levels of interleukin-6, interleukin-8, C-reactive protein, lactate dehydrogenase, D-dimer and aspartate aminotransferase 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.

Two control groups with similar entry criteria and baseline characteristics were used for retrospective comparison, both showing substantial mortality rates at 32% and 53%

Discussions are progressing between Omeros and offices in the Department of Health and Human Services, including the Biomedical Advanced Research and Development Authority (BARDA), along with the National Institutes of Health Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program regarding potential funding to accelerate large-scale manufacturing to enable broader availability of narsoplimab for COVID-19 patients and for other COVID-19-related programmatic activities.

Narsoplimab, also known as "OMS721," is an investigational human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), a novel pro-inflammatory protein target and the effector enzyme of the lectin pathway of complement. Importantly, in clinical studies, inhibition of MASP-2 has not appeared to interfere with the antibody-dependent classical complement activation pathway, which is a critical component of the acquired immune response to infection.

Omeros controls the worldwide rights to MASP-2 and all therapeutics targeting MASP-2.

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 programmes are also in progress for narsoplimab in immunoglobulin A nephropathy, and in atypical hemolytic uremic syndrome.

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.
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