Table 2.
Anti-TFPI Antibodies that Entered Clinical Trials
| Anti-TFPI Antibody (Company) | Characteristics | Bioavailability (for s.c. Administration) | Ongoing Clinical Trials | Completed Clinical Trials | Frequency, Route, and Dose in Active Trials | Mean ABR | Immunogenicity |
|---|---|---|---|---|---|---|---|
| Concizumab, mAb 2021 (Novo Nordisk) | murine mAb, humanized (IgG4); epitope within the K2 domain of TFPI | 93%74,75 | phase 2 (ClinicalTrials.gov: NCT03196297): efficacy and safety of once daily prophylaxis in patients with severe hemophilia A without inhibitors phase 2 (ClinicalTrials.gov: NCT03196284):efficacy of once daily prophylaxis in hemophilia A and B patients with inhibitors |
phase 1 (ClinicalTrials.gov: NCT02490787): multiple dose, safety, PK, and PD of concizumab in hemophilia A subjects | once daily s.c., loading dose 0.5 mg/kg followed by 0.15 mg/kg (with potential stepwise dose escalation to 0.25 mg/kg) | 7 (ClinicalTrials.gov: NCT03196297, hemophilia A without inhibitors) 4.5 (ClinicalTrials.gov: NCT03196284, hemophilia A and B with inhibitors) |
ADAs detected in 6/53 (3 NAbs) participants of ClinicalTrials.gov: NCT03196297 and NCT03196284 studies, none of which caused a loss of efficacy73 |
| Marstacimab, PF-06741086 (Pfizer) | fully human (IgG1) mAb, selected from a phage display library of scFvs derived from non-immunized human donors and converted to IgG1; epitope within the K2 domain of TFPI | 100% (in cynomolgus)76 | phase 2 (ClinicalTrials.gov: NCT03363321): safety, tolerability, and efficacy of long-term treatment in subjects with severe hemophilia A and B with or without inhibitors | phase 1 (ClinicalTrials.gov: NCT02531815): safety, tolerability, PK, and PD of single ascending dose in healthy subjects only; phase 2 (ClinicalTrials.gov: NCT02974855): safety, tolerability, PK, and PD multiple doses in subjects with severe hemophilia A and B, with or without inhibitors |
once weekly s.c., 3 doses tested: 150 mg (after the first loading dose of 300 mg), 300 mg (no loading dose), and 450 mg (no loading dose) | – | ADAs detected in 15/32 (3 NAbs) participants of ClinicalTrials.gov: NCT02531815 study; all NAbs (3) detected 42 days after administration, when the drug effects had already dissipated, so impact on PK and PD unknown77 |
| BAY 1093884 (Bayer) | fully human (IgG2) mAb, selected from a phage display library of scFvs derived from non-immunized human donors and converted to IgG2; epitope encompasses K1 and K2 domains of TFPI78 | 52% or 61% depending on the assay (in cynomolgus)79 | none (phase 2 ClinicalTrials.gov: NCT03597022 study has just been terminated due to serious adverse events) | phase 1 (ClinicalTrials.gov: NCT02571569): safety, tolerability, and PK of increasing single doses and multiple doses in subjects with severe hemophilia A or B, with or without inhibitors phase 1 (ClinicalTrials.gov: NCT03481946): PK and PD in patients with severe hemophilia A and B, with or without inhibitors |
– | – | no data |
| MG1113 (Green Cross) | murine mAb, humanized (IgG4)80 | no data | phase 1 (ClinicalTrials.gov: NCT03855696): safety and tolerability of a single ascending dose in hemophilia A and B patients without inhibitors and healthy subjects | N/A | single dose s.c. and i.v., six doses: 0.5 mg/kg (s.c.), 1.7 mg/kg (s.c.), 3.3 mg/kg (s.c. and i.v.), 6.6 mg/kg (i.v.) in healthy subjects; 3.3 mg/kg (s.c.), 6.6 mg/kg, and 13.3 mg/kg (i.v.) in hemophilia subjects | – | N/A |
ABR, annualized bleeding rate; mAb, monoclonal antibody; s.c., subcutaneous(ly); Ig, immunoglobulin; scFv, single-chain variable fragment; TFPI, tissue factor pathway inhibitor; PK, pharmacokinetics; PD, pharmacodynamics; NAb, neutralizing antibody, ADA, anti-drug antibody; N/A, not applicable.