AKCEA-APO(a)-LRx lowers Lp(a) levels in patients

AKCEA-APO(a)-LRx therapy reduces lipoprotein(a) (Lp(a)) levels in a dose-dependent manner in patients with established cardiovascular disease, according to a phase II trial. AKCEA-APO(a)-LRx is an antisense oligonucleotide targeting LPA mRNA (which encodes the main Lp(a) constituent, apolipoprotein(a)) conjugated with triantennary N-acetylgalactosamine to direct the therapy specifically to hepatocytes. A total of 286 patients with high levels of Lp(a) (≥60 mg/dl) and pre-existing cardiovascular disease were randomly assigned to receive AKCEA-APO(a)-LRx at different doses or placebo for 6–12 months. All doses induced significant reductions in Lp(a) levels compared with placebo, with the highest dose (20 mg weekly) inducing a mean 80% reduction. At the highest cumulative dose regimen (equivalent to 80 mg monthly), 98% of patients achieved Lp(a) levels ≤50 mg/dl.


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  1. Tsimikas, S. et al. Lipoprotein(a) reduction in persons with cardiovascular disease. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa1905239 (2020)

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Correspondence to Irene Fernández-Ruiz.

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Fernández-Ruiz, I. AKCEA-APO(a)-LRx lowers Lp(a) levels in patients. Nat Rev Cardiol 17, 132 (2020). https://doi.org/10.1038/s41569-020-0336-5

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