Blood Journal
Leading the way in experimental and clinical research in hematology

Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura

  1. Filip Callewaert1,*,
  2. Jan Roodt2,3,*,
  3. Hans Ulrichts1,
  4. Thomas Stohr1,
  5. Walter Janse van Rensburg2,
  6. Seb Lamprecht2,
  7. Stefaan Rossenu1,
  8. Sofie Priem1,
  9. Wouter Willems4, and
  10. Josefin-Beate Holz4
  1. 1Pharmacology Department, Ablynx NV, Zwijnaarde, Belgium;
  2. 2Department of Haematology and Cell Biology, University of the Free State, Bloemfontein, South Africa;
  3. 3Department of Haematology, National Health Laboratory Service Tertiary Laboratory, Universitas Hospital, Bloemfontein, South Africa; and
  4. 4Clinical Operations Department, Ablynx NV, Zwijnaarde, Belgium


ALX-0681 is a therapeutic Nanobody targeting the A1-domain of VWF. It inhibits the interaction between ultra-large VWF and platelet GpIb-IX-V, which plays a crucial role in the pathogenesis of thrombotic thrombocytopenic purpura (TTP). In the present study, we report the efficacy and safety profile of ALX-0681 in a baboon model of acquired TTP. In this model, acute episodes of TTP are induced by administration of an ADAMTS13-inhibiting mAb. ALX-0681 completely prevented the rapid onset of severe thrombocytopenia and schistocytic hemolytic anemia. After induction of TTP, platelet counts also rapidly recovered on administration of ALX-0681. This effect was corroborated by the full neutralization of VWF activity. The schistocytic hemolytic anemia was also halted and partially reversed by ALX-0681 treatment. Brain CT scans and post mortem analysis did not reveal any sign of bleeding, suggesting that complete neutralization of VWF by ALX-0681 under conditions of thrombocytopenia was not linked with an excessive bleeding risk. The results obtained in this study demonstrate that ALX-0681 can successfully treat and prevent the most important hallmarks of acquired TTP without evidence of a severe bleeding risk. Therefore, ALX-0681 offers an attractive new therapeutic option for acquired TTP in the clinical setting.

  • Submitted April 3, 2012.
  • Accepted August 16, 2012.
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