Table 1.

Characteristics, mechanism of action, and pharmacologic properties of FXI and FXII inhibitors

	Mechanism of action	Route of administration	Onset of action	Half-life	Administration frequency	Renal excretion	Metabolism by CYP	Potential for food and drug interactions
DNA aptamers: 11.16, 12.7, and FELIAP	Bind over large surface areas on a target protein and block specific macromolecular interactions	IV or SC	Rapid (minutes to hours)	Short (minutes to hours)	Daily	No	No	No
ASOs: IONIS FXI-Rx (ISIS 416858) and fesomersen	Inhibit the biosynthesis of FXI	SC	Slow (weeks)	Long (weeks)	Once weekly to once monthly	No	No	No
Antibodies
Abelacimab (MAA868)	Binds to the catalytic domain of FXI and locks it in the inactive zymogen conformation, preventing its activation by FXII/thrombin	IV or SC	Rapid (hours)	Long (weeks)	Once monthly	No	No	No
Osocimab (BAY 1213790)	Binds next to the active site of FXIa and inhibits the activation of factor IX	IV or SC	Rapid (hours)	Long (30-44 days)	Once monthly	No	No	No
Xisomab (AB023)	Inhibits FXIIa- mediated activation of FXI but not FXI activation by thrombin	IV	Rapid (hours)	Days to weeks, half-life increases with high doses	Once monthly	No	No	No
Garadacimab (CSL312)	Binds to the catalytic domain of FXIIa and inhibits its protease activity	IV or SC	Rapid (hours)	Long (weeks)	Once monthly	No	No	No
Small molecules
Milvexian (BMS-986177/JNJ-70033093)	Active site-directed inhibitor of FXI	Oral	Rapid (minutes to hours) Saturable absorption with doses ≥300  mg	Short (terminal half-life 8.3-13.8 hours)	Once or twice daily	Yes, <20%	Yes	Yes
Asundexian (BAY 2433334)	Active site-directed inhibitor of FXI	Oral	Rapid (minutes to hours)	Short (terminal half-life 15.8-17.8 hours)	Once daily	Yes, <15%	Yes	Yes

CYP, cytochrome P450; IV intravenous; SC, subcutaneous.