New therapies for bleeding disorders undergoing investigation in human clinical trials
| Drug . | Target disease(s) . | Mechanism . | Drug class . | Stage of clinical development . | Route of administration pharmacokinetics . | Trial results . |
|---|---|---|---|---|---|---|
| Emicizumab | Hemophilia A with and without inhibitors | FVIIIa mimetic | Bispecific humanized antibody | Phase 3 clinical trials completed | Subcutaneous half-life, 30 d | 62%-71% 0 ABR 79%-87% bleed reduction in inhibitor patients |
| Zymogen-like FXa | Hemophilia A and B with inhibitors, other bleeding disorders, and anticoagulant reversal | Bypass agent | Modified recombinant clotting factor | Phase 1 | Intravenous half-life, 4 min | Improved aPTT, thrombin generation, increased TAT complexes, prothrombin fragment 1 + 2, and D-dimer |
| Zymogen-like FIXa | Hemophilia B | Bypass agent | Modified recombinant clotting factor | Preclinical | Intravenous half-life, h | Improved hemostasis in hemophilia mouse tail clip model |
| FIXa not dependent on FVIIIa cofactor activity | Hemophilia A with inhibitors | Bypass agent | Modified Recombinant clotting factor | Preclinical | Intravenous half-life, h | Shortened aPTT and improved hemostasis in hemophilia mouse tail clip model |
| Fitusiran | Hemophilia A and B with inhibitors and other bleeding disorders | Targeting natural anticoagulant pathway | GalNAC-siRNA | Phase 2 clinical trial ongoing | Subcutaneous, administered monthly | 48% 0 ABR in mixed hemophilia A and B inhibitor population |
| TFPI | Hemophilia A and B with inhibitors and other bleeding disorders | Targeting natural anticoagulant pathway | Monoclonal antibodies, antibody fragment, | Phase 1 clinical trial published | Subcutaneous half-life, 1-5 d | Increased D-dimer and prothrombin fragments |
| Mutant α1 antitrypsin | Hemophilia A and B with inhibitors and other bleeding disorders | Targeting natural anticoagulant pathway | Modified recombinant clotting factor | Preclinical | Intravenous half-life, 5-7 d | Improved thrombin generation and improved hemostasis in hemophilia mouse tail clip model |
| rVWF | Von Willebrand disease | Factor replacement | Recombinant clotting factor | FDA approved | Intravenous half-life, 21.9 h | 96.9% good or excellent bleed control in 192 bleeds |
| Drug . | Target disease(s) . | Mechanism . | Drug class . | Stage of clinical development . | Route of administration pharmacokinetics . | Trial results . |
|---|---|---|---|---|---|---|
| Emicizumab | Hemophilia A with and without inhibitors | FVIIIa mimetic | Bispecific humanized antibody | Phase 3 clinical trials completed | Subcutaneous half-life, 30 d | 62%-71% 0 ABR 79%-87% bleed reduction in inhibitor patients |
| Zymogen-like FXa | Hemophilia A and B with inhibitors, other bleeding disorders, and anticoagulant reversal | Bypass agent | Modified recombinant clotting factor | Phase 1 | Intravenous half-life, 4 min | Improved aPTT, thrombin generation, increased TAT complexes, prothrombin fragment 1 + 2, and D-dimer |
| Zymogen-like FIXa | Hemophilia B | Bypass agent | Modified recombinant clotting factor | Preclinical | Intravenous half-life, h | Improved hemostasis in hemophilia mouse tail clip model |
| FIXa not dependent on FVIIIa cofactor activity | Hemophilia A with inhibitors | Bypass agent | Modified Recombinant clotting factor | Preclinical | Intravenous half-life, h | Shortened aPTT and improved hemostasis in hemophilia mouse tail clip model |
| Fitusiran | Hemophilia A and B with inhibitors and other bleeding disorders | Targeting natural anticoagulant pathway | GalNAC-siRNA | Phase 2 clinical trial ongoing | Subcutaneous, administered monthly | 48% 0 ABR in mixed hemophilia A and B inhibitor population |
| TFPI | Hemophilia A and B with inhibitors and other bleeding disorders | Targeting natural anticoagulant pathway | Monoclonal antibodies, antibody fragment, | Phase 1 clinical trial published | Subcutaneous half-life, 1-5 d | Increased D-dimer and prothrombin fragments |
| Mutant α1 antitrypsin | Hemophilia A and B with inhibitors and other bleeding disorders | Targeting natural anticoagulant pathway | Modified recombinant clotting factor | Preclinical | Intravenous half-life, 5-7 d | Improved thrombin generation and improved hemostasis in hemophilia mouse tail clip model |
| rVWF | Von Willebrand disease | Factor replacement | Recombinant clotting factor | FDA approved | Intravenous half-life, 21.9 h | 96.9% good or excellent bleed control in 192 bleeds |
aPTT, activated partial thromboplastin time; FDA, US Food and Drug Administration; GalNAC, N-acetylgalactosamine; TAT, thrombin antithrombin complexes.