University of Kansas a Leading Site in Clinical Trial Assessing Drug Affecting High Cholesterol from Genes

University of Kansas a Leading Site in Clinical Trial Assessing Drug Affecting High Cholesterol from Genes

A clinical investigator from the University of Kansas School of Medicine, Patrick M. Moriarty, co-led a clinical trial testing a drug focusing on individuals who have inherited a condition subjecting them to high cholesterol irrespective of diet or lifestyle. The University of Kansas Health System has one of the largest Lipid-apheresis programs in North America and emerged as a leading site in this multicenter, multinational clinical trial.


Published in the New England Journal of Medicine, the study results reveal that experimental drug PO(a)-LRx reduced lipoprotein(a) levels in a dose-dependent manner in patients who had elevated lipoprotein(a) levels and established cardiovascular disease.

Health Challenge

Lipoprotein(a), or Lp(a) is made up of apo(a) protein bound to LDL cholesterol and contains oxidized phospholipids, resulting in an atherogenic, pro-inflammatory and thrombogenic lipoprotein. Elevated Lp(a) is recognized as an independent, genetic cause of cardiovascular disease present in approximately 20-30% of the population. Lp(a) levels are determined at birth, and therefore, lifestyle modifications such as diet and exercise don’t impact Lp(a) levels.

Current Treatments

The only known therapies to successfully lower LP(a) and risk of cardiovascular disease include PCSK9 inhibitors (PCSK9i) and Lipid-apheresis. An injectable administered one time every couple of weeks, PCSK9i can lower LDL and Lp(a). The reduction of Lp(a) with PCSK9i unfortunately isn’t consistent, however it can range in reduction rate from 15 to 30%.

As reported by the Hays Post, for the past couple of decades, lipid-apheresis therapy has been approved and accepted by both private insurance and Medicare. This approved treatment can lower the amount of LDL and Lp(a) by 70%. Treatments are typically once every two weeks and last two to three hours.

In an additional study at lead investigator Moriarty’s clinic, the University of Kansas-based team demonstrated that the use of apheresis can reduce the risk of another cardiovascular event.

The Study

Funded by Akcea Therapeutics, the Phase II study represented a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, including tolerability of the experimental drug—ISIS 681257—as well as to assess the efficacy of different doses and dosing regimens of ISIS 681257 for reduction of Lp(a) levels in patients with hyperlipoproteinemia(a) and established cardiovascular disease. Targeting 286 participants, the study included sites in multiple countries. Akcea is an affiliate to the parent company of Ionis Pharmaceuticals. Participants were given injections—receiving either a placebo of saline solution or the experimental drug in varying amounts.

For participants to qualify, they needed to not only have a history of cardiovascular problems but also elevated levels of LP(a).

The Results

The participants who received 20 milligrams of the investigative drug once a month for six months experienced a 35% reduction in lipoprotein(a). Those who took that same dose weekly saw a reduction of 80%.

The Drug

ISIS 681257 or AKCEA-APO(a)-LRx is an antisense drug that uses Ionis’ advanced Ligand Conjugated Antisense or LICA technology. The drug inhibits the production of apolipoprotein(a), or Apo(a), protein, thereby reducing Lp(a). This particular drug targets the creation of the protein that carries cholesterol. If the U.S. Food and Drug Administration (FDA) eventually approves the drug, it could aid in the lowering of a specific type of cholesterol found in the blood and hence contribute to lowering the risk of cardiovascular-based life-threatening conditions.

Lead Research/Investigator

Patrick M. Moriarty, MD, director of Clinical Pharmacology and the Atherosclerosis/Lipid-apheresis Center, professor of internal medicine, University of Kansas School of Medicine

Call to Action: A Phase III clinical trial is apparently in the works. Dr. Moriarty reports the investigative team (and sponsor) will look “at very hard endpoints here” such as “heart attack, stroke, death—the whole nine yards.” TrialSite News will monitor this forthcoming study and include any updates in the daily newsletter.