Targeting a Key Marker of Clotting and Inflammation in COVID-19 Patients

Coronavirus 2019 (COVID-19) has shown it can predisposition patients to thrombotic disease. With the development of this complication, it can worsen a patient’s condition, and make for a more severe case for clinicians to treat.

“In those with elevated thrombosis…while they have COVID-19 disease have worse outcomes,” Charles Bruen, MD, a critical care and emergency physician at Regions Hospital in St. Paul, MN., said. “Not only do we have to address the respiratory difficulties that patients have, but also the clotting disorders.”

D-dimer, a protein fragment that demonstrates clotting and inflammation, can be elevated in COVID-19 patients and has also been associated with higher mortality.

San Diego-based CalciMedica, a clinical-stage biotechnology company, which develops therapies for severe acute and chronic inflammatory diseases, is looking to address thrombosis by reducing elevated D-dimer levels. CalciMedica has developed Auxora, a therapy targeting calcium release-activated calcium (CRAC) channels.

In small study results thus far, the investigational therapy has shown it can reduce D-dimer levels.

Auxora is being studied in a blinded, placebo-controlled trial that is enrolling up to 400 ventilated patients with severe COVID-19 pneumonia at up to 40 sites. Patients will receive either Auxora or matched lipid nano-emulsion placebo in addition to standard of care.

The company presented its findings thus far at the recent Critical Care Congress. In its study, 17 patients with severe COVID-19 pneumonia were randomized to receive Auxora plus standard of care, and 9 patients received standard of care alone. The standard of care at study sites included prophylactic anticoagulation.

The results showed that levels of D-dimer decreased in patients receiving Auxora combined with standard of care therapy but increased in patients receiving standard of care alone. In addition, 2 patients who received standard of care alone developed femoral deep vein thrombosis, with 1 patient progressing to a pulmonary embolism. None of the patients who received Auxora developed thromboembolic disease.

Bruen has served as a Auxora trial investigator, and spoke to Contagion recently about Auxora’s mechanism of action, the therapy’s regimen, and details of the ongoing trial.