On Oct. 15, 2020, Ionis Pharmaceuticals announced that IONIS-PKK-LRx was being evaluated in an investigator-initiated Phase 2 clinical study to determine its effectiveness in reducing the severity of respiratory complications in patients with COVID-19. The trial at the Hospital do Coracao, Sao Paulo, Brazil will enroll up to 110 patients at 25 hospitals. Ionis provided IONIS-PKK-LRx and funding to the Brazilian Research for Intensive Care Network (BRICNet) to support the study.

IONIS-PKK-L_Rx is designed to inhibit bradykinin signaling by halting synthesis of prekallikrein (PKK), a precursor of the enzyme kallikrein, which is involved in the formation of bradykinin, a protein that promotes inflammation and dilates blood vessels. There is growing evidence that the pulmonary edema (fluid in the lungs) and associated morbidities in severe COVID-19, such as the respiratory distress syndrome, are, in part, caused by a dysregulation in bradykinin signaling, referred to as a “bradykinin storm”. A therapy that prevents or reduces this bradykinin storm could potentially decrease the number of severe cases of COVID-19 in Brazil.

In the study, a single dose of IONIS-PKK-L_Rx or placebo will be administered subcutaneously to hospital patients who present with symptoms consistent with COVID-19. The primary endpoint is the number of days alive and free of oxygen support up to 15 days.