Caplacizumab: a change in the paradigm of thrombotic thrombocytopenic purpura treatment

Expert Opin Biol Ther. 2019 Nov;19(11):1127-1134. doi: 10.1080/14712598.2019.1650908. Epub 2019 Aug 5.

Abstract

Introduction: Immune thrombotic thrombocytopenic purpura (iTTP) is an immune-mediated deficiency in von Willebrand factor-cleaving protease ADAMTS13 allowing unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis. Caplacizumab, an anti-von Willebrand factor humanized, bivalent single-domain nanobody preventing its binding to the platelet has been investigated and approved for use in the treatment of iTTP. Areas covered: The purpose of this article is to summarize the available clinical data on the efficacy and safety of caplacizumab in iTTP and to provide our opinion on the place of caplacizumab in current treatment regimens. Expert opinion: Caplacizumab is a new drug with a complementary mechanism of action with respect to the standard available therapeutics. It demonstrated efficacy in clinical trials through a faster platelet count normalization and protection of patients from exacerbations and refractoriness. Caplacizumab is well tolerated with minor bleeds as the most important side effect. The efficacy of caplacizumab now needs to be assessed in real-life but definitely, this drug opens hope for a significant improvement in iTTP prognosis at the very early, critical step of the disease.

Keywords: ADAMTS13; Caplacizumab; targeted therapy; thrombotic thrombocytopenic purpura; von Willebrand factor.

Publication types

  • Review

MeSH terms

  • ADAMTS13 Protein / immunology
  • ADAMTS13 Protein / metabolism
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Hemorrhage / drug therapy
  • Hemorrhage / metabolism
  • Humans
  • Plasma Exchange
  • Product Surveillance, Postmarketing / methods
  • Prognosis
  • Purpura, Thrombotic Thrombocytopenic / diagnosis
  • Purpura, Thrombotic Thrombocytopenic / drug therapy*
  • Purpura, Thrombotic Thrombocytopenic / immunology
  • Purpura, Thrombotic Thrombocytopenic / metabolism
  • Single-Domain Antibodies / chemistry
  • Single-Domain Antibodies / pharmacology
  • Single-Domain Antibodies / therapeutic use*
  • von Willebrand Factor / immunology

Substances

  • Single-Domain Antibodies
  • von Willebrand Factor
  • caplacizumab
  • ADAMTS13 Protein
  • ADAMTS13 protein, human