Remaining challenges in the hemophilia treatment landscape, possible solutions, and novel agents in the pipeline
| Remaining challenges . | Possible solutions . | Novel agents . |
|---|---|---|
| Burden of prophylaxis | Subcutaneous delivery | Factor 8 |
| N8-GP | ||
| Factor 9 | ||
| BIVV002 | ||
| Substitutive | ||
| Emicizumab | ||
| Rebalancing | ||
| AT: fitusiran | ||
| TFPI: concizumab, PF-06741086, BAY1093884 | ||
| APC: SerpinPC | ||
| PS: PS siRNA | ||
| Oral delivery | Expression within plant cells | |
| pH-responsive anionic complexation hydrogels | ||
| Immunogenicity | Eliminate nonhuman glycan epitopes, expression in human cell lines | Human cl-rhFVIII |
| Enhance affinity to VWF via nanobody technology | FVIII-KB013bv | |
| Use of nonfactor modalities | All substitutive and rebalancing therapies | |
| Extended time to tolerization | Exploit immune-modulatory and tolerogenic properties of Fc fragment | rFVIIIFc |
| Breakthrough bleeding | Resistance to anticoagulant inhibition | FIX variant CB2679d |
| Increased affinity for cofactor | FIX variant CB2679d | |
| Target steady-state hemostatic control | Substitutive | |
| Emicizumab | ||
| Rebalancing | ||
| AT: fitusiran | ||
| TFPI: concizumab, PF-06741086, BAY1093884 | ||
| APC: SerpinPC | ||
| PS: PS siRNA |
| Remaining challenges . | Possible solutions . | Novel agents . |
|---|---|---|
| Burden of prophylaxis | Subcutaneous delivery | Factor 8 |
| N8-GP | ||
| Factor 9 | ||
| BIVV002 | ||
| Substitutive | ||
| Emicizumab | ||
| Rebalancing | ||
| AT: fitusiran | ||
| TFPI: concizumab, PF-06741086, BAY1093884 | ||
| APC: SerpinPC | ||
| PS: PS siRNA | ||
| Oral delivery | Expression within plant cells | |
| pH-responsive anionic complexation hydrogels | ||
| Immunogenicity | Eliminate nonhuman glycan epitopes, expression in human cell lines | Human cl-rhFVIII |
| Enhance affinity to VWF via nanobody technology | FVIII-KB013bv | |
| Use of nonfactor modalities | All substitutive and rebalancing therapies | |
| Extended time to tolerization | Exploit immune-modulatory and tolerogenic properties of Fc fragment | rFVIIIFc |
| Breakthrough bleeding | Resistance to anticoagulant inhibition | FIX variant CB2679d |
| Increased affinity for cofactor | FIX variant CB2679d | |
| Target steady-state hemostatic control | Substitutive | |
| Emicizumab | ||
| Rebalancing | ||
| AT: fitusiran | ||
| TFPI: concizumab, PF-06741086, BAY1093884 | ||
| APC: SerpinPC | ||
| PS: PS siRNA |