US-based Isis Pharmaceuticals has started a Phase I clinical trial of ISIS-ANGPTL3Rx, an antisense drug targeting angiopoietin-like 3 protein (ANGPTL3), an independent risk factor for the treatment of cardiovascular disease.
Around 48 healthy volunteers will be enrolled in the blinded, placebo-controlled, dose-escalation Phase I trial, which will evaluate the safety, tolerability and pharmacokinetics of both single and multiple doses of ISIS-ANGTPL3Rx.
The company said that by reducing ANGPTL3, ISIS-ANGPTL3Rx, which is designed to act as a broad dyslipidemia agent, has the potential to reduce LDL-cholesterol and triglycerides, and to increase insulin sensitivity.
The trial is designed to assess 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.
University of California professor of medicine and director of vascular medicine Dr Sotirios Tsimikas said that 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," Tsimikas said.
"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."
According to the company, in preclinical studies, it has observed significant reductions of LDL-cholesterol and triglycerides associated with reductions in ANGPTL3.
The company said that it has also observed reduced atherosclerosis in a mouse model of atherosclerosis.
Isis vice president of development and chief medical officer Dr Walter Singleton said, "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."
Image: A 4ml sample of hyperlipidemic blood with lipids separated into the top fraction (sample is in an EDTA collection tube). Photo courtesy of Mark-shea.