Summary of novel therapies for patients with hemophilia and inhibitors currently in clinical trial
| Category . | Agent . | Mechanism of action . | Administration . | Drug half-life . | Clinical trial status . |
|---|---|---|---|---|---|
| “Targeting the on switch” | Emicizumab (ACE910) | Bispecific antibody binds fIXa and fX mimicking fVIIIa to generate thrombin | Subcutaneous injection (weekly vs monthly dosing) | ∼30 d (healthy subjects) | Preclinical completed50 |
| Phase 1 completed30 | |||||
| Phase 2/3 ongoing | |||||
| “Targeting the off switch” | Fitusiran (ALN-AT3) | Antithrombin knockdown via siRNA interference of hepatic AT3 mRNA translation and gene expression | Subcutaneous injection | 7 d | Phase 1 ongoing36,37,51 |
| Phase 2/3 due to enroll in 2017 | |||||
| Concizumab (MAb 2021) | TFPI inhibitor | Subcutaneous injection or intravenous infusion | 7 d | Preclinical completed38 | |
| Phase 1 completed39 | |||||
| Other agents | rfVIIa-FP (CSL689) | Extended half-life rfVIIa and albumin fusion protein | Intravenous infusion | ∼6-10 h | Preclinical completed42 |
| Phase 1 completed43 | |||||
| Phase 2/3 enrolling | |||||
| Obizur (OBI-1, BAX801) | B-domain deleted porcine factor replacement product | Intravenous infusion (on-demand dosing) | ∼10-12 h48 (patients with hemophilia A) | US Food and Drug Administration approved 2014 for acquired hemophilia A (U.S.) | |
| Reduced cross-reactivity with anti-human fVIII inhibitors | Estimations will vary, depending on the presence of underlying cross-reactive antibodies | Phase 1-3 completed for acquired hemophilia A indication | |||
| Phase 1/2 in patients with congenital hemophilia A and inhibitors completed48,49 |
| Category . | Agent . | Mechanism of action . | Administration . | Drug half-life . | Clinical trial status . |
|---|---|---|---|---|---|
| “Targeting the on switch” | Emicizumab (ACE910) | Bispecific antibody binds fIXa and fX mimicking fVIIIa to generate thrombin | Subcutaneous injection (weekly vs monthly dosing) | ∼30 d (healthy subjects) | Preclinical completed50 |
| Phase 1 completed30 | |||||
| Phase 2/3 ongoing | |||||
| “Targeting the off switch” | Fitusiran (ALN-AT3) | Antithrombin knockdown via siRNA interference of hepatic AT3 mRNA translation and gene expression | Subcutaneous injection | 7 d | Phase 1 ongoing36,37,51 |
| Phase 2/3 due to enroll in 2017 | |||||
| Concizumab (MAb 2021) | TFPI inhibitor | Subcutaneous injection or intravenous infusion | 7 d | Preclinical completed38 | |
| Phase 1 completed39 | |||||
| Other agents | rfVIIa-FP (CSL689) | Extended half-life rfVIIa and albumin fusion protein | Intravenous infusion | ∼6-10 h | Preclinical completed42 |
| Phase 1 completed43 | |||||
| Phase 2/3 enrolling | |||||
| Obizur (OBI-1, BAX801) | B-domain deleted porcine factor replacement product | Intravenous infusion (on-demand dosing) | ∼10-12 h48 (patients with hemophilia A) | US Food and Drug Administration approved 2014 for acquired hemophilia A (U.S.) | |
| Reduced cross-reactivity with anti-human fVIII inhibitors | Estimations will vary, depending on the presence of underlying cross-reactive antibodies | Phase 1-3 completed for acquired hemophilia A indication | |||
| Phase 1/2 in patients with congenital hemophilia A and inhibitors completed48,49 |