Pharmacokinetics, pharmacodynamics, and safety of fesomersen, a novel antisense inhibitor of factor XI, in healthy Chinese, Japanese, and Caucasian volunteers
© 2024 Bayer AG. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics..
The inhibition of coagulation factor XI (FXI) presents an attractive approach for anticoagulation as it is not expected to increase the risk of clinically relevant bleeding and is anticipated to be at least as effective as currently available anticoagulants. Fesomersen is a conjugated antisense oligonucleotide that selectively inhibits the expression of FXI. The article describes three clinical studies that investigated the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of fesomersen after subcutaneous (s.c.) injection to healthy participants. The studies included participants from diverse ethnic backgrounds (Caucasian, Japanese, and Chinese). Fesomersen demonstrated good safety and tolerability in all three studies. No major bleeding events were observed. After single-dose s.c. injection, fesomersen was rapidly absorbed into the systemic circulation, with maximum fesomersen-equivalent (fesomersen-eq) concentrations (Cmax) in plasma observed within a few hours. After reaching Cmax, plasma fesomersen-eq concentrations declined in a biphasic fashion. The PD analyses showed that the injection of fesomersen led to dose-dependent reductions in FXI activity and increases in activated partial thromboplastin time (aPTT). The maximum observed PD effects were reached between Day 15 and 30, and FXI activity and aPTT returned to near-baseline levels by Day 90 after a single dose. The PK/PD profiles after a single injection were similar among the various ethnic groups. Collectively, the study results suggest that fesomersen has a favorable safety profile and predictable and similar PK and PD profiles across Chinese, Japanese, and Caucasian participants.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
Clinical and translational science - 17(2024), 4 vom: 02. Apr., Seite e13784 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Tianxing [VerfasserIn] |
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| Links: |
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| Themen: |
9013-55-2 |
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| Anmerkungen: |
Date Completed 03.04.2024 Date Revised 17.04.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1111/cts.13784 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370529170 |
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| 245 | 1 | 0 | |a Pharmacokinetics, pharmacodynamics, and safety of fesomersen, a novel antisense inhibitor of factor XI, in healthy Chinese, Japanese, and Caucasian volunteers |
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| 520 | |a The inhibition of coagulation factor XI (FXI) presents an attractive approach for anticoagulation as it is not expected to increase the risk of clinically relevant bleeding and is anticipated to be at least as effective as currently available anticoagulants. Fesomersen is a conjugated antisense oligonucleotide that selectively inhibits the expression of FXI. The article describes three clinical studies that investigated the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of fesomersen after subcutaneous (s.c.) injection to healthy participants. The studies included participants from diverse ethnic backgrounds (Caucasian, Japanese, and Chinese). Fesomersen demonstrated good safety and tolerability in all three studies. No major bleeding events were observed. After single-dose s.c. injection, fesomersen was rapidly absorbed into the systemic circulation, with maximum fesomersen-equivalent (fesomersen-eq) concentrations (Cmax) in plasma observed within a few hours. After reaching Cmax, plasma fesomersen-eq concentrations declined in a biphasic fashion. The PD analyses showed that the injection of fesomersen led to dose-dependent reductions in FXI activity and increases in activated partial thromboplastin time (aPTT). The maximum observed PD effects were reached between Day 15 and 30, and FXI activity and aPTT returned to near-baseline levels by Day 90 after a single dose. The PK/PD profiles after a single injection were similar among the various ethnic groups. Collectively, the study results suggest that fesomersen has a favorable safety profile and predictable and similar PK and PD profiles across Chinese, Japanese, and Caucasian participants | ||
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| 700 | 1 | |a Hashizume, Kensei |e verfasserin |4 aut | |
| 700 | 1 | |a Krieg, Eva |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Huijun |e verfasserin |4 aut | |
| 700 | 1 | |a Mukaida, Yuki |e verfasserin |4 aut | |
| 700 | 1 | |a Thelen, Kirstin |e verfasserin |4 aut | |
| 700 | 1 | |a Friedrichs, Frauke |e verfasserin |4 aut | |
| 700 | 1 | |a Willmann, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Schwers, Stephan |e verfasserin |4 aut | |
| 700 | 1 | |a Solms, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Rosie |e verfasserin |4 aut | |
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