FDA-Approved Drug to Treat Rare Diseases of Overactive Immune System Could Help Critically Ill COVID-19 Patients

Researchers are investigating whether a drug approved by the Food and Drug Administration (FDA) to treat rare diseases of an overactive immune system could help critically ill patients hospitalized with COVID-19.

The drug, called ravulizumab, blocks a specific protein of the immune system that doctors suspect contributes to dangerous responses triggered by coronavirus infection in the lungs, kidneys and blood vessels. Ravulizumab is a monoclonal antibody that inhibits what is called the complement system, which sits at the intersection of the body’s immune responses to infection and the coagulation cascade that controls blood clotting. However, the delicate balancing act that the complement system maintains in the body can potentially go wrong in some people fighting off a severe coronavirus infection to which their bodies have no history of exposure.


Researchers at the Washington University School of Medicine (St. Louis, MO, USA) reviewed evidence that SARS-CoV-2, the virus that causes COVID-19, triggers the complement system in multiple ways and that patients who develop life-threatening COVID-19 complications fail to dial back complement after the initial viral infection is brought under control. Such patients with COVID-19 have problems that closely resemble those of patients with rare genetic disorders of the complement system. These problems include increased coagulation that can cause dangerous blood clots throughout the body, including in the vessels of the lungs, kidney, heart and brain. Additionally, one of the genetic diseases that leads to complement overdrive, atypical hemolytic uremic syndrome, causes damage to the kidneys in ways that appear similar to the kidney damage sometimes seen in patients with severe COVID-19.

The Washington University School of Medicine will be among 50 sites across four countries participating in a clinical trial of ravulizumab, led and sponsored by Alexion Pharmaceuticals, which makes the drug under the brand name Ultomiris. The trial will examine ravulizumab’s potential as a treatment for critically ill patients hospitalized with COVID-19. The clinical trial will be held at 50 sites across four countries and enroll 270 adult patients worldwide. COVID-19 patients who are admitted to intensive care units and need large amounts of oxygen because of severe pneumonia, lung damage or acute respiratory distress syndrome will be randomly assigned to receive either intravenous ravulizumab plus best supportive care or standard best supportive care alone.

“We are utilizing this FDA-approved drug for patients with severe lung complications from COVID-19 because the problems that some of these patients have appear similar to those of patients with these two genetic diseases, in which the complement system has gotten out of control,” said Hrishikesh S. Kulkarni, MD, principal investigator of the trial at Washington University and an assistant professor of medicine in the Division of Pulmonary & Critical Care Medicine. “There is evidence that activation of the complement system is at least partially responsible for some of the organ damage we see in patients with COVID-19. We believe blocking this activation is a viable approach to investigate.”

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Washington University School of Medicine