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ASH 2021: Spotlighting ADAMTS13 replacement therapy innovation

Björn Mellgård, Global Program Lead, Rare Genetic and Hematology Therapeutic Area Unit, Takeda

December 10, 2021

As a patient-driven, science-first organization, Takeda’s focus will always be on delivering life-changing treatments to patients with the greatest unmet needs. As part of our commitment to hematology, we continually explore treatments with transformative potential which may improve patient care across multiple rare and life-threatening blood disorders.

Bringing the hematology community together

The 63rd American Society of Hematology (ASH) Annual Meeting is a key opportunity for Takeda to unite with the global hematology community in sharing the latest scientific advances and research.

At this year’s gathering, Takeda has nine abstracts available at ASH covering our extensive hematology portfolio and promising pipeline;1 this research is a testament to our ongoing resolve to improve the standard of care across rare hematologic disorders.

Meeting the needs of patients with TTP

Our work in the rare, life-threatening disorder thrombotic thrombocytopenic purpura (TTP) is a key focus this year. Patients with the disease have enduring unmet needs.2,3

Symptoms and clinical signs of TTP are caused by deficiency in ADAMTS13 activity, a von Willebrand factor (VWF) cleaving protease.2,3 This deficiency results in the accumulation of VWF molecules which trigger spontaneous formation of clots in small blood vessels, which in turn reduces blood flow and can cause serious and ongoing damage to major organs.4,5,6 People living with TTP often experience an ongoing disease burden, which may be due to co-morbidities that can impact patients’ quality-of-life.7

TTP’s impact on patients is serious, extensive and chronic.2 Given the extent of the organ involvement, patients with TTP have shortened lifespans.8

Currently, the main treatment for TTP is plasma-based therapy, either by infusion or plasma exchange (PEX), with the addition of immunosuppressive and the option of antibody therapy for immune-mediated TTP (iTTP).9 Plasma therapy is time-consuming and can be associated with severe treatment complications.10

Takeda is leading new research to investigate the therapeutic potential of recombinant ADAMTS13 replacement therapy for TTP patients.5,11

At ASH, we are publishing the design of a phase 3b open-label continuation study that aims to evaluate the long-term safety and efficacy of recombinant ADAMTS13 replacement therapy for prophylactic and on-demand treatment of severe congenital thrombotic thrombocytopenic purpura (cTTP).1 cTTP is the ultra-rare genetic form of the condition.2,12,13

A potential treatment targeting ADAMTS13 deficiency would mark real and valuable progress for patients with TTP, and the wider hematology community.

A commitment to innovation

Access to new treatments is not the only factor we must address to improve outcomes for patients with TTP. It is 20 years since the role of ADAMTS13 deficiency in TTP was first discovered, yet the hematology community remains in need of wider and easier access to ADAMTS13 diagnostic testing.3 Timely and accurate diagnosis is critical in TTP to facilitate rapid treatment initiation and appropriate management.3 Wider consensus on adequate levels of ADAMTS13 may also assist diagnosis and acute, as well as long-term management of the condition. 

Takeda is firmly focused on furthering the understanding the balance between ADAMTS13 and VWF in clotting-related disorders, to explore the full therapeutic potential of recombinant replacement therapy. Sickle Cell Disease (SCD), for instance, is another disease where it may hold promise.14,15

An imbalance of ADAMTS13 and von Willebrand factor (VWF) is associated with the vaso-occlusive crises in SCD, which can cause pain, organ damage, and a shortened lifespan.15,16 The potential role recombinant ADAMTS13 may have in addressing this is the subject of a poster presentation at ASH,1 which highlights the design of the first Phase 1 study assessing safety, tolerability, pharmacokinetics, and pharmacodynamics of recombinant ADAMTS13 in patients with SCD.

Takeda's efforts to progress the science of ADAMTS13 replacement in TTP and SCD epitomize our commitment to pursue genuine treatment innovation in the areas of high unmet need. Through collaboration with the wider hematology community, particularly at key forums like ASH, I am optimistic we will collectively continue to make real headway on reducing the burden and mortality caused by these diseases.


1 Takeda. Takeda to present 23 company-sponsored abstracts at the 63rd American Society of Hematology (ASH) Annual Meeting. Available at: https://www.takeda.com/en-us/our-stories/innovation/takeda-to-present-23-company-sponsored-abstracts/

2 Kremer-Hovinga JA et al. Nat Rev Dis Prim. 2017;3:1–17

3 Joly BS et al. Blood. 2017;129(21):2836–2846

4 Chiasakul T and Cuker A. Am Soc Hematol. 2018;2018(1):530–538

5 Scully M, et al. Blood. 2014;142(2):211–219

6 Rogers HJ, et al. Cleve Clin J Med. 2016;83(8):597–603

7 Chaturvedi S et al. Blood 2014;124:230

8 Masias C et al. Res Pract Thromb Haemost. 2018;2:19-26

9 Zheng XL et al. 2020;18:2496-2502

10 McGuckin S et al. Vox Sanguinis 2014;106:161-66

11 Clinical trials. A Study of TAK-755 in Participants With Congenital Thrombotic Thrombocytopenic Purpura (NCT04683003). Available at: https://clinicaltrials.gov/ct2/show/NCT04683003. Accessed: December 2021

12 Mansouri TM et al. Hamostaseologie. 2013;33(2):138-143

13 Knöbl P. Semin Thromb Hemost. 2014;40:493-502

14 ASH 2021. Abstract [3118]. Recombinant ADAMTS13 for Patients with Sickle Cell Disease: Design of a Phase 1 Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics study

15 Sins et al J Thromb Haemost 2017;15:1392-1402 and Novelli et al Haematologica 2013;98:e132-4

16 Osunkwo et al Ther Adv Hematol 2020;11;2040620720955000