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 |
| . | 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.