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 |