Isis Pharmaceuticals Initiates Phase 1 Study of ISIS-ANGPTL3 Rx to Treat Hyperlipidemia

In Press Release by Cameron


March 19, 2014

Isis Pharmaceuticals, Inc. 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. ISIS-ANGPTL3Rx is designed to act as a broad dyslipidemia agent.  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.

“ANGPTL3 is a genetically validated target.  We know that humans who have loss-of-function mutations in ANGPTL3 exhibit lower levels of LDL-cholesterol and triglycerides and also display increased insulin sensitivity,” said Sotirios Tsimikas, M.D., Professor of Medicine, Director of Vascular Medicine,University of California, San Diego.  “Patients with dyslipidemia often have multiple cardiovascular and metabolic risk factors.  As such, treating these patients can be challenging and involve multiple different treatment regimens.  These patients would benefit tremendously from a drug that could provide benefit across multiple cardiovascular risk factors, like LDL-cholesterol and triglycerides, which are often too high despite currently available drugs.”

“In preclinical studies, we observed significant reductions of LDL-cholesterol and triglycerides associated with reductions in ANGPTL3.  We also observed reduced atherosclerosis in a mouse model of atherosclerosis,” said Walter Singleton, M.D., vice president of development and chief medical officer at Isis.  “We are developing ISIS-ANGPTL3Rx as a broad dyslipidemia agent.  Based on our preclinical data, we believe that reducing ANGPTL3 could have a beneficial impact on many lipid parameters, including LDL-cholesterol, triglycerides, total-cholesterol as well as effects on insulin sensitivity and other metabolic parameters.”

The Phase 1 study of ISIS-ANGPTL3Rx is a blinded, placebo-controlled, dose-escalation study in approximately 48 healthy volunteers.  The study is designed to assess the safety, tolerability and pharmacokinetics of both single and multiple doses of ISIS-ANGTPL3Rx.

See the press release here.