Raised Lp(a) Slashed in CV Patients on Novel Antisense Agent: Top-Line Results

September 24, 2018

Treatment with a proprietary antisense agent was associated with significant reductions in levels of lipoprotein(a) in a phase 2 study of patients with established coronary or peripheral vascular disease and elevated Lp(a), the company making the novel drug announced today in a press release.

The observed reductions in Lp(a) occurred at all tested dosage levels of the drug, called AKCEA-APO(a)-LRx (Akcea/Ionis), formerly ISIS 681257, and at several dosing frequencies that included once-monthly in the placebo-controlled study.

"Most patients in the active group achieved Lp(a) reductions below the established threshold of risk for cardiovascular disease events," according to the company statement of cursory top-line results, released in advance of a more detailed presentation scheduled for November 10 at the American Heart Association 2018 Scientific Sessions.

The ligand-conjugated antisense (LICA) agent AKCEA-APO(a)-LRx lowers levels of Lp(a), which can be genetically elevated, by inhibiting production of apolipoprotein(a). The drug was developed jointly by Akcea and Ionis Pharmaceuticals.

The double-blind study randomly assigned 286 patients with clinical coronary artery disease, stroke, or peripheral vascular disease and Lp(a) levels of at least 60 mg/dL to receive the antisense agent or placebo on top of standard therapy. The leading primary end point was percent change in plasma Lp(a) over 6 months. Some patients were treated for a year, the press release states.

The randomization groups, which included five patients assigned to AKCEA-APO(a)-LRx for every one assigned to the control group, tested dosages that ranged from 20 mg to 60 mg given from every 2 weeks to every 4 weeks.

There was no observed difference in "treatment-emergent adverse events," another prespecified primary end point. The most common, the company says, was reaction at the injection site. Low platelet levels were observed at similar rates in actively treated and control patients.

"Approximately 90% of patients completed treatment and the rate of treatment discontinuation was comparable between the active and placebo groups," the company stated.

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