Isis Pharmaceuticals announces positive results from Phase 1 study of ISIS-PKK Rx for HAE treatment

Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced today positive results from a Phase 1 study with ISIS-PKKRx. In this study, healthy volunteers treated with ISIS-PKKRx achieved dose-dependent reductions of up to 95 percent in prekallikrein, or PKK. ISIS-PKKRx is a RNA-targeted antisense drug designed to inhibit the production of PKK for the prophylactic treatment of hereditary angioedema (HAE). HAE is a severe and rare genetic disease that is characterized by rapid and painful attacks of inflammation in the hands, feet, limbs, face, abdomen, larynx and trachea. HAE affects approximately 20,000 patients in the United States and Europe and can be fatal if swelling occurs in the airway.

"Despite currently available prophylactic therapies, we believe that there remains a significant need for patients with HAE. PKK is a protein produced in the liver that plays an important role in the activation of inflammatory mediators associated with acute attacks of HAE. Since the inappropriate activation of PKK leads to HAE, these data could be predictive of the potential benefit we hope to see in patients with HAE," said Brett Monia, Ph.D., senior vice president of antisense drug discovery at Isis Pharmaceuticals. "We are very encouraged with these early clinical data demonstrating that ISIS-PKKRx can significantly and dose-dependently lower its target, PKK. In addition to the robust PKK lowering we observed in this study, ISIS-PKKRx was well tolerated and the safety profile observed to date supports our plan to evaluate ISIS-PKKRx as prophylaxis for patients who suffer from HAE attacks. We plan to initiate a Phase 2 study later this year."

The Phase 1 study of ISIS-PKKRx was a blinded, placebo-controlled, dose-escalation study in healthy volunteers. The study was designed to assess the safety, tolerability and pharmacokinetics of ISIS-PKKRx. ISIS-PKKRx was evaluated in single and multiple doses ranging from 50 mg per week up to 400 mg per week for the single dose and 100 mg up to 400 mg for the multiple doses. After only 3 weeks of dosing, subjects in the 100, 200, 300 and 400 mg multiple-dose cohorts displayed a mean reduction of PKK of 33, 69, 87 and 92 percent, respectively, from baseline. In this study, ISIS-PKKRx was generally well tolerated.

"ISIS-PKKRx is a new addition to our severe and rare disease franchise, and one that we plan to develop into later-stage clinical studies on our own. We have the internal resources and capabilities to easily and rapidly move this program forward in patients with HAE," said B. Lynne Parshall, chief operating officer at Isis Pharmaceuticals. "ISIS-PKKRx is also a product of our improved second generation, or generation 2-plus, technology, which enables us to consistently develop more potent and better tolerated drugs."


Isis Pharmaceuticals, Inc.


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