Repositioning Candidate Details
| Candidate ID: | R0921 |
| Source ID: | DB06081 |
| Source Type: | approved; investigational |
| Compound Type: | biotech |
| Compound Name: | Caplacizumab |
| Synonyms: | Caplacizumab; caplacizumab-yhdp |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank Description: | Caplacizumab, firstly called ALX-0081, is a humanized single-variable-domain immunoglobulin consisting of two identical humanized building blocks genetically linked by a three-alanine linker. Caplacizumab was developed by Ablynx, a Sanofi company and FDA approved on February 6, 2019, and approved previously by the EU in October 2018 as a combination therapy with plasma exchange and immunosuppression. |
| CAS Number: | 915810-67-2 |
| Molecular Weight: | |
| DrugBank Indication: | Capacizumab is approved for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP) in conjunction with plasma exchange and immunosuppression in patients 18 years or older. aTTP is a rare autoimmune condition presented by a disruption of blood clotting order which is translated into systemic microvascular thrombosis leading to profound thrombocytopenia, hemolytic anemia and organ ischemia. It is caused by the production of autoantibodies against ADAMTS-13 which is the protein in charge of cleaving the von-Wilebrand factor. The lack of this process produces the generation of ultra large von Wilebrand multimers that bind to platelets and form microthrombi and causing thromboembolic complications. Previously, capacizumab was under review for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention but this indication was withdrawn. |
| DrugBank Pharmacology: | _In vitro_ studies have shown a caplacizumab-driven complete inhibition of platelet aggregation and in phase II clinical trials, it was shown to reduce the activity of the von Willebrand factor by 20% from treatment day 1 until treatment day 30. The level of von Willebrand factor in the plasma was also significantly reduced due to the clearance of the von Willebrand-caplacizumab complex. In phase III clinical trials, more than 50% of the tested individuals reached a platelet normal count. In these trials, it was observed as well a significant reduction in the incidence of aTTP as well as a significant reduction in the median time to response of about 39%. However, as caplacizumab does not target autoimmune response, relapses were observed after treatment discontinuation. The last clinical trial prior approval showed production of a platelet count of more than 150,000 per mcl after the cessation of plasma exchange therapy for 5 days as well as a reduction of patient recurrent thrombotic thrombocytopenic purpura and of disease-related death during treatment. |
| DrugBank MoA: | Caplacizumab acts by targetting the A1 domain of the ultra-large von Willebrand factor which in order inhibits the interaction with the glycoprotein Ib-IX-V receptor in the platelets. Caplacizumab binds to von Willebrand factor with an affinity of 8.5 nM, thus it is very target specific. The blockage of the von Willebrand factor prevents the interaction between the von Willebrand factor and the platelets, hence, preventing platelet aggregation. |
| Targets: | von Willebrand factor |
| Inclusion Criteria: | Therapeutic strategy associated |
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