Flekarsen is a liver-targeted antisense oligonucleotide that potently reduces lipoprotein(a) levels. [Lp(a)]. So far, no extensive research has been done on the safety and effectiveness of the treatment in diverse populations. In a study whose findings were published in the journal ‘Journal of Clinical Lipidology’, the aim of the researchers was to evaluate the effect of flukarsen, including at a monthly dose of 80 milligrams, among subjects of Japanese origin.
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For this purpose, the researchers conducted a randomized double-blind and in vivo controlled study in 29 healthy Japanese subjects, who were treated with single ascending dosesJ (SAD) of flakersen in doses of 20, 40 and 80 milligrams subcutaneously, or with multiple dosesJ(MD) of flakersen at a dose of 80 milligrams every month, up to four doses in total. The primary outcome of the study was an assessment of safety and tolerability in healthy Japanese subjects; Secondary outcomes included the evaluation of flekkersen pharmacokinetics; And the exploratory outcome was defined as the determination of the effect of flekkersen on plasma Lp(a) levels.
As part of the study, no serious adverse events or clinically relevant disorders were recorded in all laboratory parameters. The mean plasma concentration of flekkersen in the MD group peaked at approximately 4 hours, and declined biexponentially thereafter. In the SAD cohorts, it was found that the percentage of changes in Lp(a) corrected in the inbo-corrected least-square mean (PCLSM) on day 30 of the study were -55.4% (p=0.0008), -58.9% (p=0.0003), and 73.7% (p<0.0001) for the groups treated with 20 milligrams, 40 milligrams and 80 milligrams of flakersen, respectively. In the MD group, the PCLSM on days 29, 85, 113, 176 and 204 of the study were -84.0% (p=0.0003), -106.2% (p<0.0001), -70.0 (p<0.0001), -80.0% (p=0.0104), and -55.8% (p=0.0707), respectively.
In conclusion, Flekersen demonstrates a satisfactory safety and tolerability profile, and led to a significant reduction of plasma Lp(a) levels in healthy subjects of Japanese origin. These findings were also observed under a monthly dose of 80 milligrams which was evaluated in the Lp(a) HORIZON trial.
source:
Karwatowska-Prokopczuk E, Lesogor A, Yan JH, Hurh E, Hoenlinger A, Margolskee A, Xia S, Tsimikas S. Efficacy and safety of pelacarsen in lowering Lp(a) in healthy Japanese subjects. J Clin Lipidol. 2022 Dec 8:S1933-2874(22)00337-3. doi: 10.1016/j.jacl.2022.12.001. Epub ahead of print. PMID: 36529659.