Research by University of Iowa virologist Wendy Maury, PhD, has helped facilitate the launch of a new clinical trial in the United Kingdom of a drug that might help treat patients with COVID-19.
The drug, known as bemcentinib, was developed by BerGenBio ASA, a clinical-stage biopharmaceutical company based in Bergen, Norway. Bemcentinib is a small molecule inhibitor that targets a cell protein called AXL. BerGenBio has developed bemcentinib as a potential treatment for certain cancers. But work from Maury's lab and others has shown that AXL has another role; it is one of several cell surface receptors used by different enveloped (lipid encased) viruses to enter cells.
Maury's new studies suggest that the enveloped Coronavirus, SARS-CoV-2, which causes COVID-19, uses AXL to enter into some cells, and that bemcentinib profoundly inhibits virus entry into those cells. These preclinical findings suggest that bemcentinib is potentially useful for the treatment of early SARS-CoV-2 infection.
"Viruses must enter cells to replicate and my lab has previously shown that AXL is one of several cell surface receptors used by different enveloped viruses to enter cells," explains Maury, professor of microbiology and immunology at the UI Carver College of Medicine. "Ebola virus and Zika virus use this type of receptor. We have now shown that SARS-CoV-2 uses AXL to enter multiple cell types; a finding that may explain some of the disease symptoms caused by SARS-CoV-2."
Maury's role in the new work grew from a collaboration she has with James Lorens, professor of biomedicine at the University of Bergen and Chief Scientific Officer of BerGenBio. Both research groups have a shared interest in AXL. Maury's group focuses on AXL's role as a receptor for enveloped viruses, whereas Lorens' group studies the role of AXL in tumor formation and metastasis. Based on Lorens' work, BerGenBio has developed novel, selective AXL kinase inhibitors, including bemcentinib, which has been tested in clinical trials for certain cancers and has been shown to be safe and well-tolerated in hundreds of patients.
Given the dual role of AXL, it was logical to test bemcentinib's antiviral activity against the SARS-CoV-2 virus.
"Our longstanding research collaboration with Dr. Maury, along with her expertise in this area and the University of Iowa's capability to work with the SARS-CoV-2 virus, was an ideal opportunity for us to rapidly test the effect of bemcentinib on this virus," Lorens says.
"The combination of our very positive data on the drug's ability to inhibit viral entry into cells, coupled with all of the safety work and clinical trial testing that Dr. Lorens and BerGenBio have completed on the drug, has paved the way for testing of this drug in patients with COVID-19," adds Maury, who has a contract with BerGenBio for this research.
Bemcentinib has been selected to undergo rapid testing in an urgent public health research study (ACCORD) for the treatment of hospitalized National Health Service (NHS) patients with COVID-19. Funded by the UK Department of Health and Social Care (DHSC) and the UK Research and Innovation (UKRI), the ACCORD study is a multi-center, seamless, Phase II adaptive randomization platform trial to assess the efficacy and safety of multiple candidate agents for the treatment of COVID 19 in hospitalized NHS patients. The trial will rapidly commence testing and will enroll 120 subjects (60 hospitalized COVID-19 patients and 60 control group receiving standard of care treatment) across six UK NHS hospital trusts.