Experimental drug aims to prevent blood clots without boosting risk of bleeding

Conventional anti-clotting drugs have a big downside: increased risk of internal bleeding. An entirely new class of antithrombotic developed at OHSU and its spin-off biopharmaceutical company, Aronora, aims to eliminate bleeding complications. 

A phase 2 clinical trial at OHSU in Portland, Oregon, is testing whether the drug works in preventing catheter-associated blood clots in patients with cancer receiving chemotherapy, says principal Investigator Joseph Shatzel, M.D. He’s an assistant professor of medicine in the OHSU School of Medicine with appointments in the Knight Cancer Institute and Department of Biomedical Engineering. The trial has been funded, in part, by the National Heart, Lung and Blood Institute of the National Institute of Health.

The investigational drug, xisomab 3G3, is a recombinant antibody that binds to a specific site on a blood enzyme called factor XI. When bound there, it blocks the activation of factor XI by another blood clotting factor, XII, which interrupts the intrinsic contact activation pathway of blood coagulation. But the antibody does not stop factor XI from contributing to the extrinsic pathway that is vital for rapid clotting of blood at wound sites.

In a phase 1 trial in healthy adults, the drug produced dose-dependent anticoagulation with no bleeding complications or other high-grade adverse events. András Gruber, M.D., a professor of biomedical engineering in the OHSU School of Medicine, led the development of the drug with OHSU biomedical engineering colleague Erik Tucker, Ph.D., a research assistant professor.

The phase 2 study addresses a critical unmet need for therapies that prevent clotting on catheters. Cather-related blood clots are an important cause of morbidity and sometimes mortality in patients with cancer. Complications include pulmonary embolism, infection, catheter failure and delays in cancer treatment. Existing antithrombotic blood thinner agents such as low-molecular-weight heparin and warfarin haven’t proven both safe and effective at preventing clotting on catheters.