Antisense Drug Can Safely and Effectively Reduce Elevated Lipoprotein(a)

Researchers aimed to find the optimal dose and regimen of AKCEA-APO(a)-LRX injected subcutaneously for further clinical development.

The following article is part of conference coverage from the 2018 AHA Scientific Sessions in Chicago, Illinois. MPR’s staff will be reporting breaking news associated with research conducted by leading experts in cardiology. Check back for the latest news from AHA 2018.

CHICAGO — AKCEA-APO(a)-LRX is a safe and effective treatment for patients with established cardiovascular disease and elevated levels of lipoprotein(a) [Lp(a)], according to results of a Phase 2 study presented at the American Heart Association (AHA) Scientific Sessions 2018 on November 10 in Chicago, Illinois.1 AKCEA-APO(a)-LRX is a second-generation, N-acetyl-galactosamine-conjugated, antisense oligonucleotide targeted to apolipoprotein(a).

Elevated Lp(a) is an independent hereditary risk factor for cardiovascular disease. Researchers aimed to find the optimal dose and regimen of AKCEA-APO(a)-LRX injected subcutaneously for further clinical development in the treatment of elevated levels of Lp(a), a genetic risk factor for atherosclerotic cardiovascular disease and calcific aortic valve stenosis.

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The randomized, double-blind trial included a total of 286 patients in a 5:1 treatment ratio (AKCEA-APO[a]-LRX:placebo) to 5 cohorts treated with 20, 40, or 60mg/month; 20mg/every 2 weeks; or 20mg/week.

All patients were treated for a minimum of 6 months, and some patients were treated for up to 12 months, depending on trial entry. Approximately 90% of the patients completed treatment, with a rate of continuation at 12.1% for the AKCEA-APO(a)-LRX group and 14.9% for the placebo group.

The results of the study showed that approximately 98% of patients in the 20 mg/weekly cohort and approximately 81% of patients in the 60 mg/month achieved clinically significant reductions in Lp(a) levels.

Treatment with AKCEA-APO(a)-LRX was also associated with decreases in LDL-C, apoB, OxPL-apoB, and OxPL-apo(a).

“A drug that reduces Lp(a) could be a paradigm shift for the cardiovascular community. Physicians are looking for a tool to treat their patients who today have no pharmacological option to sustainably reduce their Lp(a) levels below 50 mg/dL, the threshold for a Lp(a)-driven cardiac event such as a heart attack or stroke,” said Sotirios Tsimikas, MD, vice president of global cardiovascular development at Ionis Pharmaceuticals; professor of medicine and director of vascular medicine at the University of California, San Diego; and an international expert in a press release.2

Dr Tsimikas discloses significant employment with Ionis Pharamaceuticals. Please refer to references for full list of disclosures.

For more coverage of AHA 2018, click here.


  1. Tsimikas S, Karwatowska-Prokopczuk E, Gouni-Berthold I, et al. Safety and efficacy of AKCEA-APO(a)-LRX to lower lipoprotein(a) levels in patients with established cardiovascular disease: a phase 2 dose-ranging trial. Presented at: AHA Scientific Sessions 2018; November 10-12, 2018; Chicago, IL. Abstract 19497.
  2. Phase 2 results on AKCEA-APO(a)-LRX presented in a late-breaking clinical trial presentation at AHA Scientific Sessions [press release]. Carlsbad, California: Ionis Pharmaceuticals. Published November 12, 2018. Accessed November 12, 2018.

This article originally appeared on The Cardiology Advisor