Spotlighting TTP research and innovation | Takeda Stories

Our work in the rare, life-threatening blood disorder, thrombotic thrombocytopenic purpura (TTP), is a key focus area for Takeda. Patients with the disease have enduring unmet needs.

Symptoms and clinical signs of TTP are caused by deficiency in ADAMTS13, an enzyme which normally cleaves large von Willebrand factor (VWF) multimers to smaller and less active fragments.¹ This enzyme deficiency results in the accumulation of the large VWF multimers, which trigger spontaneous formation of clots in small blood vessels, and in turn reduces blood flow and can cause serious and ongoing damage to major organs.^1,2,3,4 People living with TTP often experience a significant disease burden, which very often has daily impact on patients’ quality-of-life.⁵

The impact of TTP on patients is serious, extensive and chronic.¹ Acute episodes of TTP often need intensive hospital care and can be life-threatening. Given the extent of the organ involvement, patients with TTP have shortened expected lifespans.⁵

There are two forms of TTP which are defined by the underlying cause of the ADAMTS13 deficiency. In the ultra-rare congenital form (cTTP), there is a genetic defect which leads to a lifelong deficiency of the ADAMTS13 enzyme, whereas immune-mediated TTP (iTTP) is caused by the erroneous production of antibodies against ADAMTS13.

Currently, the main management option for TTP is plasma-based therapy, either by infusion or in severe or acute situations by plasma exchange (PEX). In cTTP, patients most often receive plasma-based infusion therapy, either to manage ongoing symptoms or as prophylactic therapy to prevent short- and long-term consequences. In iTTP, patients often present with an acute episode and PEX is used for the initial management of symptoms and with the addition of immunosuppressive therapies for long term management by reducing the antibody production.³ Plasma-based therapies are insufficient in fully restoring ADAMTS13 and can be time-consuming.^3,6,7

We are leading new research to investigate the therapeutic potential of recombinant ADAMTS13 replacement therapy for TTP patients.^8,9

In January 2023 we announced the favourable safety and efficacy data for enzyme replacement therapy with recombinant ADAMTS13 from the first and only controlled Phase 3 trial in congenital TTP (cTTP).

The results of this study were presented in detail at the International Society on Thrombosis and Haemostasis (ISTH) 2023 Congress, further adding to the body of knowledge for cTTP and the potential role of ADAMTS13 replacement therapy in this ultra-rare blood clotting disorder.¹⁰

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

Access to new and improved treatments is not the only factor we must address to improve outcomes for patients with TTP. It has been 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.⁴ Timely and accurate diagnosis is critical in acute TTP to facilitate appropriate management and treatment initiation. Wider consensus on adequate levels of ADAMTS13 may also assist diagnosis in acute and long-term management of the condition.

We are firmly focused on furthering understanding the balance between ADAMTS13 and VWF in clotting-related disorders, to explore the full therapeutic potential of recombinant ADAMTS13 replacement therapy. Through our ongoing clinical development program, we are hopeful that we will make real headway on reducing the burden and mortality caused by these diseases.