Clinical Trials

* On November 15, 2016, Akcea Therapeutics, a wholly-owned subsidiary of Ionis Pharmaceuticals, Inc. , today announced positive results from an interim analysis of a Phase 1/2a study of IONIS-ANGPTL3-LRx. In this study, subjects with elevated triglycerides achieved substantial and statistically significant mean reductions in angiopoietin-like 3 (ANGPTL3), triglycerides and LDL-cholesterol of up to 83 percent, 66 percent, and 35 percent, respectively. The study was presented at the American Heart Association Scientific Sessions by Sotirios Tsimikas, M.D., professor of medicine and director of vascular medicine at the University of California, San Diego, and vice president of clinical development at Ionis Pharmaceuticals.

Subjects who received multiple doses of 10 mg, 20 mg, 40 mg, or 60 mg of IONIS-ANGPTL3-LRx achieved dose-dependent, statistically significant mean reductions at Day 37 in ANGPTL3 of up to 83 percent (p ?0.001). These subjects also experienced statistically significant mean reductions in triglycerides of up to 66 percent (p ?0.001), in LDL-C of up to 35 percent (p ?0.001), and in total cholesterol of up to 36 percent (p ?0.001). In this study, IONIS-ANGPTL3-LRx displayed a favorable safety and tolerability profile. There were no discontinuations due to adverse events and no clinically meaningful platelet declines.

* On March 23, 2015, Isis Pharmaceuticals announced positive results from a Phase 1 study with ISIS-ANGPTL3Rx. In this study, healthy volunteers treated with ISIS-ANGPTL3Rx achieved dose-dependent, statistically significant reductions in angiopoietin-like 3 (ANGPTL3) of up to 93 percent with a mean reduction of up to 84 percent from baseline (p<0.001). In addition, statistically significant reductions from baseline in lipid parameters were observed, including up to 63% with a mean reduction of up to 49% (p<0.01) in triglycerides and up to 46% with a mean reduction of up to 28% (p<0.001) in total cholesterol. ANGPTL3 is a protein that acts as a key regulator of these blood lipids. These data were presented at the 83rd European Atherosclerosis Society in Glasgow, United Kingdom.

The Phase 1 study of ISIS-ANGPTL3Rx was a blinded, placebo-controlled, dose-escalation study in healthy volunteers. The study was designed to assess the safety, tolerability and pharmacokinetics of ISIS-ANGPTL3Rx. ISIS-ANGPTL3Rx 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 per week up to 400 mg per week for the multiple dose. In this study, ISIS-ANGPTL3Rx was generally well tolerated. ISIS-ANGPTL3Rx is part of Isis' lipid franchise and, as such, Akcea Therapeutics, Isis' wholly owned subsidiary, is responsible for developing ISIS-ANGPTL3Rx.

* On March 19, 2014, Isis Pharmaceuticals has announced that it has initiated a Phase 1 clinical study for ISIS-ANGPTL3Rx, an antisense drug targeting angiopoietin-like 3 protein (ANGPTL3), an independent risk factor for cardiovascular disease. By reducing ANGPTL3, ISIS-ANGPTL3Rx has the potential to reduce LDL-cholesterol and triglycerides, and to increase insulin sensitivity.  Isis plans to evaluate ISIS-ANGPTL3Rx in patients who have severe metabolic or cardiovascular disease and who would benefit from a drug that simultaneously addresses a variety of adverse lipid and metabolic parameters contributing to their disease.