Caplacizumab (Cablivi) is a humanized von Willebrand factor (vWF) targeted Nano-antibody, also known as Single Domain Antibody (SdAb) or Heavy-Chain Variable (VHH). Caplacizumab was meticulously developed by Ablynx (a subsidiary of Sanofi) and approved to treat patients with acquired thrombotic thrombocytopenic purpura (aTTP), an uncommon disorder characterized by abnormal blood clotting in small blood vessels. Caplacizumab targets the A1 domain of vWF, blocking its interaction with the platelet GpIb-IX-V receptor and preventing platelet-rich thrombi formation.
Caplacizumab, a bivalent Nanobody, is comprised of two homologous humanized units linked by a three-alanine linker. It is expressed in Escherichia coli (E. coli) through recombinant DNA technology, resulting in an approximate molecular weight of 28 kDa.
Caplacizumab is the first approved drug targeting vWF and treating acquired thrombotic thrombocytopenic purpura (aTTP). It also holds the distinction of being the first approved single-domain antibody, marking a notable milestone in small biologics.
Key Milestones of Caplacizumab
Caplacizumab was initially discovered by Ablynx, a biotechnology company founded in 2001 specializing in the development and commercialization of “nanobodies” in llamas and other camelids. In a strategic move, Sanofi completed the acquisition of Ablynx in January 2018 for €3.8 billion, triumphing over competitor Novo Nordisk, which had presented multiple offers for the company.
The efficacy and safety of caplacizumab were evaluated by positive endpoints in patients with acquired thrombotic thrombocytopenic purpura (aTTP) during both the phase 2 TITAN trial and the subsequent phase 3 HERCULES trial.
In 2018, the European Medicines Agency (EMA) granted its first approval for caplacizumab, in combination with plasma exchange and immunosuppression, to treat adults experiencing an episode of aTTP.
In February 2019, this regulatory milestone was followed by approval from the U.S. Food and Drug Administration (FDA), endorsing Sanofi's Caplacizumab for the treatment of aTTP.
Yaohai Bio-Pharma Offers One-Stop CDMO Solution for VHH/sdAb
Anti-vWF VHH Pipeline
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Generic Name
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Brand Name/ Alternative Name
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Expression System
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Indications
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Manufacturer
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R&D Stage
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Caplacizumab-YHDP
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ALX-0081, ALX-0681, Cablivi, カブリビ
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Escherichia coli
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Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
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Ablynx NV, Sanofi
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Approval
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Reference:
[1] Duggan S. Caplacizumab: First Global Approval. Drugs. 2018 Oct;78(15):1639-1642. doi: 10.1007/s40265-018-0989-0.
[2] Morrison C. Nanobody approval gives domain antibodies a boost. Nat Rev Drug Discov. 2019 Jul;18(7):485-487. doi: 10.1038/d41573-019-00104-w.
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