Ionis Pharmaceuticals, Inc. announces the publication of the results from a compassionate-use study evaluating IONIS-PKKRx and IONIS-PKK-LRx in patients living with severe bradykinin-mediated angioedema in The New England Journal of Medicine(NEJM). IONIS-PKKRx and IONIS-PKK-LRx are investigational antisense medicines designed to reduce the production of prekallikrein (PKK), which plays a key role in the activation of inflammatory mediators associated with acute attacks of HAE. In the study, researchers found that the drugs reduced plasma prekallikrein activity levels and showed evidence of clinical efficacy in reducing the number of breakthrough attacks per month in patients over the course of the treatment, including complete resolution in a patient with Type 1 HAE.

“The results of this study are encouraging and support continued development of IONIS-PKK-LRx as a potential treatment in patients with severe HAE for whom current therapies offer limited therapeutic benefit. The study also highlights the progress we continue to make advancing investigational medicines that are wholly owned by Ionis,” says Richard S. Geary, Ph.D., Executive Vice-President of Development and a co-author on the paper.

In the study, two patients – Patient 1 with Type 1 HAE and Patient 2 with Type 3 HAE – were first treated with IONIS-PKKRx for a period of 12 to 16 weeks, after which they received IONIS-PKK-LRx at a dose of 80 mg every three to four weeks for seven to eight months at the time of data analysis. During treatment with the ligand-conjugated IONIS-PKK-LRx and the unconjugated parent drug, IONIS-PKKRx, there was a clinically meaningful reduction in HAE attack rates in both patients. Plasma prekallikrein activity levels decreased substantially following treatment.

Physicians have long prescribed prophylactic treatment approaches, including C1-INH replacement therapies and more recently inhibitors of plasma kallikrein, to prevent and reduce the severity of HAE attacks. IONIS-PKK-LRx is an investigational antisense medicine that is being developed because it has the potential to provide significant efficacy with the convenience of once per month low volume subcutaneous injections.
(Source: Ionis)