Novel targeted therapies for TTP
| Therapy . | Mechanism/target . | Supporting evidence . |
|---|---|---|
| Rituximab | Suppress anti-ADAMTS13 antibody by depleting CD20-positive B cells | Retrospective and prospective studies show benefit in acute TTP and for relapse prevention (Table 1) |
| Caplacizumab | Nanobody directed toward the A1 domain of VWF inhibits VWF’s interaction with platelet GP1b-IX-V receptors | Phase 2 and 3 trials demonstrated reduced time to platelet normalization, lower exacerbation rates, and reduction in mean PEX procedures and hospital length of stay compared with placebo |
| NAC | Cleaves VWF multimers by reducing disulfide linkages | Reduction in VWF multimer size and VWF-dependent platelet aggregation in preclinical models |
| Case reports of successful use in refractory TTP | ||
| Bortezomib | Reduction in anti-ADAMSTS13 antibody production through apoptotic destruction of plasma cells | Case reports and series of successful use in patients refractory to multiple lines of therapy |
| Recombinant ADAMTS13 | Neutralization of anti-ADAMSTS13 antibodies and restoration of ADAMSTS13 activity | Phase 1 trial demonstrated safety in congenital TTP; phase 3 trial planned |
| Anfibatide | Reduces platelet–VWF interaction through antagonism of the platelet GP1b receptor | Inhibited platelet–VWF aggregate formation in in vitro studies and resolved thrombocytopenia in a mouse model of TTP |
| Therapy . | Mechanism/target . | Supporting evidence . |
|---|---|---|
| Rituximab | Suppress anti-ADAMTS13 antibody by depleting CD20-positive B cells | Retrospective and prospective studies show benefit in acute TTP and for relapse prevention (Table 1) |
| Caplacizumab | Nanobody directed toward the A1 domain of VWF inhibits VWF’s interaction with platelet GP1b-IX-V receptors | Phase 2 and 3 trials demonstrated reduced time to platelet normalization, lower exacerbation rates, and reduction in mean PEX procedures and hospital length of stay compared with placebo |
| NAC | Cleaves VWF multimers by reducing disulfide linkages | Reduction in VWF multimer size and VWF-dependent platelet aggregation in preclinical models |
| Case reports of successful use in refractory TTP | ||
| Bortezomib | Reduction in anti-ADAMSTS13 antibody production through apoptotic destruction of plasma cells | Case reports and series of successful use in patients refractory to multiple lines of therapy |
| Recombinant ADAMTS13 | Neutralization of anti-ADAMSTS13 antibodies and restoration of ADAMSTS13 activity | Phase 1 trial demonstrated safety in congenital TTP; phase 3 trial planned |
| Anfibatide | Reduces platelet–VWF interaction through antagonism of the platelet GP1b receptor | Inhibited platelet–VWF aggregate formation in in vitro studies and resolved thrombocytopenia in a mouse model of TTP |