Clinical pharmacology of caplacizumab for the treatment of patients with acquired thrombotic thrombocytopenic purpura

• Published in: Expert review of clinical pharmacology Vol. 12; no. 6; pp. 537 - 545
• Main Authors: Sargentini-Maier, Maria Laura, De Decker, Philip, Tersteeg, Claudia, Canvin, Jan, Callewaert, Filip, De Winter, Hilde
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.06.2019
• Subjects: Administration, Intravenous; aTTP; Caplacizumab; clinical pharmacology; Drug Interactions; exposure-response relationship; Fibrinolytic Agents - administration & dosage; Fibrinolytic Agents - adverse effects; Fibrinolytic Agents - therapeutic use; Humans; Hypodermoclysis; Nanobod y; pharmacodynamics; pharmacokinetics; Plasma Exchange - methods; Purpura, Thrombotic Thrombocytopenic - drug therapy; Purpura, Thrombotic Thrombocytopenic - physiopathology; RICO; Single-Domain Antibodies - administration & dosage; Single-Domain Antibodies - adverse effects; Single-Domain Antibodies - therapeutic use; Time Factors; vWF; Nanobod y; aTTP; vWF; RICO; pharmacodynamics; pharmacokinetics; clinical pharmacology; exposure–response relationship; Caplacizumab
• ISSN: 1751-2433; 1751-2441
• DOI: 10.1080/17512433.2019.1607293

Introduction: Caplacizumab is a humanized anti-von Willebrand Factor (vWF) Nanobody® for the treatment of acquired Thrombotic Thrombocytopenic Purpura (aTTP). Caplacizumab targets the A1-domain of vWF, inhibiting the interaction between vWF and platelets. Clinical studies conducted in aTTP patients confirmed the rapid and sustained complete suppression of the vWF activity using an initial intravenous dose of 10 mg, and a maintenance subcutaneous 10 mg daily dosing regimen, with corresponding favorable efficacy and safety profiles. Areas covered: The pharmacokinetics of caplacizumab are non-linear, characterized by a target-mediated disposition and the exposure is dependent upon drug and target concentration over time. The pharmacokinetics of caplacizumab are predictable when considering the turn-over of the circulating vWF and its modulation by the drug over time. Renal and hepatic impairment are not expected to influence the exposure to the drug, and no direct or indirect drug-drug pharmacokinetic interactions are anticipated based on the mechanism of action and the specificity of the pharmacodynamic effect of caplacizumab. Expert opinion: Caplacizumab prevents the interaction between vWF and platelets, offering a direct and rapid therapeutic intervention to stop microthrombosis. The combination of caplacizumab with plasma exchange and immunosuppression represents an important, potentially life-saving advance in the treatment of aTTP patients.