IONIS-PKK-LRx from Ionis Pharmaceuticals, Inc. is 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 coordinators are Fernando G. Zampieri, M.D., Ph.D., and Alexandre Biasi Cavalcanti, M.D., Hospital do Coracao (HCor Research Institute), Sao Paulo, Brazil. The study will enroll up to 110 patients at 25 hospitals in Brazil. Ionis has provided IONIS-PKK-LRx and funding to the Brazilian Research for Intensive Care Network (BRICNet) to support the study.
IONIS-PKK-LRx 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.
“Bradykinin elevations in the body can cause blood vessels to become leaky, causing inflammation in the surrounding tissue. In the lungs, this is often associated with severe COVID-19 cases. We are hopeful that IONIS-PKK-LRx can alleviate some of the worst symptoms caused by the infection and we look forward to seeing data from the study,” says Kenneth Newman, M.D., M.B.A., Ionis’ vice president of clinical development and leader of the pulmonology and immunology franchise.
In the study, a single dose of IONIS-PKK-LRx 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.
IONIS-PKK-LRx is also undergoing a Phase 2 clinical study in patients with HAE. In September 2020, the New England Journal of Medicine published encouraging data showing safety and efficacy in two patients with uncontrolled, severe HAE. These data support the continued development of IONIS-PKK-LRx as a potential treatment in patients with severe HAE for whom current therapies offer limited therapeutic benefit.
IONIS-PKK-LRx is one of 20 potentially transformative antisense programs in the growing Ionis-owned pipeline that the company is prioritizing and preparing for commercialization.(Source: Ionis)