Isis Begins Phase I Of Hyperlipidemia Drug ISIS-ANGPTL3Rx Trial

Isis Pharmaceuticals Inc. announced that it has started the Phase I clinical study for its hyperlipidemia drug ISIS-ANGPTL3Rx.

ISIS-ANGPTL3Rx is an antisense drug that works to target angiopoietin-like 3 protein (ANGPTL3), considered an independent risk factor for cardiovascular disease. The drug is designed to act as a broad dyslipidemia agent. ISIS-ANGPTL3Rx can potentially reduce LDL-cholesterol and triglycerides, and to increase insulin sensitivity through reduction of ANGPTL3.

Walter Singleton, vice president of development and chief medical officer at Isis, said “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. 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 company announced its plans to evaluate ISIS-ANGPTL3Rx in eligible patients who have severe metabolic or cardiovascular disease, and who stands to gain benefits from a drug that addresses several adverse lipid and metabolic parameters linked to their disease simultaneously.

Sotirios Tsimikas, professor of medicine and director of vascular medicine at the University of California, San Diego, said “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. 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.”

The drug’s safety, tolerability, and pharmacokinetics will be evaluated in a blinded, placebo controlled, dose escalation Phase I study involving about 48 patients.