16 October 2020 - - US-based antisense therapeutics developer Ionis Pharmaceuticals, Inc's (NASDAQ: IONS) IONIS-PKK-LRx 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 company said.

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, 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-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.

Learn more about the Phase 2 study here: Antisense Therapy to Block the Kallikrein-kinin Pathway in COVID-19 (ASKCOV).

IONIS-PKK-LRx is also undergoing a Phase 2 clinical study in patients with hereditary angioedema. In September, 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.

IONIS-PKK-LRx is an investigational antisense medicine designed to reduce the production of prekallikrein, or PKK, in patients with hereditary angioedema, or HAE, a rare, genetic, potentially fatal disease characterized by rapid and painful attacks of inflammation in the hands, feet, limbs, face, abdomen, larynx and trachea.

IONIS-PKK-LRx was developed using Ionis' advanced LIgand Conjugated Antisense technology platform. PKK plays an important role in the activation of inflammatory mediators associated with acute attacks of HAE.

Current prophylactic treatment approaches are limited and have major tolerability issues, leaving patients with few therapeutic options. IONIS-PKK-LRx is also undergoing an investigator-initiated Phase 2 clinical study in Brazil to evaluate its effectiveness in reducing the severity of respiratory complications in patients with COVID-19.