| Protein . | Name . | Modification . | Clinical status* . | Reference(s) . |
|---|---|---|---|---|
| Protein replacement strategies | ||||
| FVIII | wt FVIII | Pegylated liposomes | No increase in T1/2; phase 3 completed | 17, 18, 55 |
| N8-GP | Single 40 kDa PEG attached to 21 amino acid B-domain | Well-tolerated; in phase 3 | 31 | |
| BAX855 | ∼ 2 mol PEG/full-length FVIII | ∼ 1.5× increased T1/2; in phase 1 | 29 | |
| BAY94–9027 | 60 kDa PEG attached to single site in A3-domain | In phase 3 | 24, 28 | |
| rFVIII-Fc | FcIg fusion to rFVIII | ∼ 1.5-2× increased T1/2; phase 3 completed | 36, 56 | |
| scFVIII | Single chain FVIII | ∼ 1.14× increased T1/2 | 41 | |
| rhFVIII h-cl | rFVIII manufactured in a human cell line | In clinical trials | 44, 45 | |
| FIX | N9-GP | 40 kDa PEG attached to activation peptide | 5× increased T1/2; phase 3 completed | 33, 57 |
| Fc-FIX | FcIg fusion protein to FIX | ∼ 3-4× increased T1/2; phase 3 finished | 37 | |
| rFIX-FP | rFIX fusion to albumin | ∼ 5× increased T1/2; in phase 3 | 39, 40 | |
| Bypassing strategies | ||||
| FVIIa | N7-GP | 40 kDa attached to 1 glycan | Characterization stopped due to lack of effect | 32 |
| rFVIIa-FP | hFVIIa fusion to albumin | ∼ 5× increased T1/2 in clinical trials | 38, 58 | |
| mAb | hBS23 Xase mimetic | Bispecific mAb binds FIXa and FX | Preclinical | 47 |
| TFPI | mAb 2012 | mAb binds TFPI kringle 2 to inhibit | Preclinical | 48 |
| BAX499 | Nucleic acid aptamer to inhibit TFPI | Characterization stopped | 49 | |
| BAX513 | Sulfated polysaccharide | Characterization stopped | 50 | |
| AT | ALN-AT3 | siRNA targeting antithrombin 3 | Preclinical | 54 |
| Protein . | Name . | Modification . | Clinical status* . | Reference(s) . |
|---|---|---|---|---|
| Protein replacement strategies | ||||
| FVIII | wt FVIII | Pegylated liposomes | No increase in T1/2; phase 3 completed | 17, 18, 55 |
| N8-GP | Single 40 kDa PEG attached to 21 amino acid B-domain | Well-tolerated; in phase 3 | 31 | |
| BAX855 | ∼ 2 mol PEG/full-length FVIII | ∼ 1.5× increased T1/2; in phase 1 | 29 | |
| BAY94–9027 | 60 kDa PEG attached to single site in A3-domain | In phase 3 | 24, 28 | |
| rFVIII-Fc | FcIg fusion to rFVIII | ∼ 1.5-2× increased T1/2; phase 3 completed | 36, 56 | |
| scFVIII | Single chain FVIII | ∼ 1.14× increased T1/2 | 41 | |
| rhFVIII h-cl | rFVIII manufactured in a human cell line | In clinical trials | 44, 45 | |
| FIX | N9-GP | 40 kDa PEG attached to activation peptide | 5× increased T1/2; phase 3 completed | 33, 57 |
| Fc-FIX | FcIg fusion protein to FIX | ∼ 3-4× increased T1/2; phase 3 finished | 37 | |
| rFIX-FP | rFIX fusion to albumin | ∼ 5× increased T1/2; in phase 3 | 39, 40 | |
| Bypassing strategies | ||||
| FVIIa | N7-GP | 40 kDa attached to 1 glycan | Characterization stopped due to lack of effect | 32 |
| rFVIIa-FP | hFVIIa fusion to albumin | ∼ 5× increased T1/2 in clinical trials | 38, 58 | |
| mAb | hBS23 Xase mimetic | Bispecific mAb binds FIXa and FX | Preclinical | 47 |
| TFPI | mAb 2012 | mAb binds TFPI kringle 2 to inhibit | Preclinical | 48 |
| BAX499 | Nucleic acid aptamer to inhibit TFPI | Characterization stopped | 49 | |
| BAX513 | Sulfated polysaccharide | Characterization stopped | 50 | |
| AT | ALN-AT3 | siRNA targeting antithrombin 3 | Preclinical | 54 |
Clinical status can be found at www.clinicaltrials.gov.