A Phase 1 Study Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of Zerlasiran in Japanese Participants
Abstract
AIM: Zerlasiran is an N-acetylgalactosamine-conjugated small interfering RNA that targets lipoprotein(a), a risk factor for atherosclerosis and calcific aortic stenosis. Zerlasiran has not been studied in Japanese participants previously. METHOD: This was an open-label, single-dose trial that enrolled 18 adult participants with lipoprotein(a) levels ≥ 70 nmol/L at a single site in Japan to evaluate subcutaneous doses of zerlasiran (30 mg, 100 mg, and 300 mg) in three ascending-dose cohorts. The participants were monitored for 150 days post-dose to assess the systemic pharmacokinetics, pharmacodynamics (lipoprotein (a) and lipid biomarkers), and safety. RESULTS: increased in a dose-dependent manner. The maximum median (interquartile range [IQR]) percent reduction in lipoprotein (a) in the 30 mg, 100 mg, and 300 mg cohorts were -72.8% (-79.7%, -67.1%), 88.8% (-89.5%, -84.7%), and -97.8% (-98.6, -96.9%), respectively, between days 30 and 60, with a sustained effect observed at 150 days at all dose levels. All adverse events were mild and self-limiting. CONCLUSION: Zerlasiran was well tolerated with no significant safety findings observed at any dose level. A typical pharmacokinetic profile expected of an N-acetylgalactosamine-conjugated small interfering RNA, coupled with a potent and sustained reduction in lipoprotein(a), was observed in Japanese participants. No adverse effects on either the liver or kidney function were observed.
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BibTeX
@article{fok2026phase,
title = {{A Phase 1 Study Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of Zerlasiran in Japanese Participants}},
author = {Henry Fok and Mariko Harada-Shiba and David Rider and Yasuko Owada and Curtis Rambaran},
journal = {Journal of Atherosclerosis and Thrombosis},
year = {2026},
month = sep,
doi = {10.5551/jat.66214},
url = {https://www.jstage.jst.go.jp/article/jat/33/9/33_66214/_article},
note = {CC BY-NC-SA},
}
RIS
TY - JOUR
TI - A Phase 1 Study Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of Zerlasiran in Japanese Participants
AU - Henry Fok
AU - Mariko Harada-Shiba
AU - David Rider
AU - Yasuko Owada
AU - Curtis Rambaran
PY - 2026
DA - 2026/09/01
JO - Journal of Atherosclerosis and Thrombosis
DO - 10.5551/jat.66214
UR - https://www.jstage.jst.go.jp/article/jat/33/9/33_66214/_article
AB - AIM: Zerlasiran is an N-acetylgalactosamine-conjugated small interfering RNA that targets lipoprotein(a), a risk factor for atherosclerosis and calcific aortic stenosis. Zerlasiran has not been studied in Japanese participants previously. METHOD: This was an open-label, single-dose trial that enrolled 18 adult participants with lipoprotein(a) levels ≥ 70 nmol/L at a single site in Japan to evaluate subcutaneous doses of zerlasiran (30 mg, 100 mg, and 300 mg) in three ascending-dose cohorts. The participants were monitored for 150 days post-dose to assess the systemic pharmacokinetics, pharmacodynamics (lipoprotein (a) and lipid biomarkers), and safety. RESULTS: increased in a dose-dependent manner. The maximum median (interquartile range [IQR]) percent reduction in lipoprotein (a) in the 30 mg, 100 mg, and 300 mg cohorts were -72.8% (-79.7%, -67.1%), 88.8% (-89.5%, -84.7%), and -97.8% (-98.6, -96.9%), respectively, between days 30 and 60, with a sustained effect observed at 150 days at all dose levels. All adverse events were mild and self-limiting. CONCLUSION: Zerlasiran was well tolerated with no significant safety findings observed at any dose level. A typical pharmacokinetic profile expected of an N-acetylgalactosamine-conjugated small interfering RNA, coupled with a potent and sustained reduction in lipoprotein(a), was observed in Japanese participants. No adverse effects on either the liver or kidney function were observed.
SN - 1880-3873
SN - 1340-3478
ER -