Recombinant ADAMTS13 for Hereditary Thrombotic Thrombocytopenic Purpura

100 Years of Thrombotic Thrombocytopenic Purpura: A Story of Death and Life

“…158,159 Due to the long half-life and the low necessary plasma concentration of ADAMTS13, prophylactic therapy in cTTP will probably be sufficient with 40 U/kg every 2 weeks; dosing for acute bouts needs to be determined, but single or dual shots of the same dose may be sufficient to terminate an episode. 84,86 The usefulness of rADAMTS13 is not yet established in autoimmune TTP, especially in patients with high titers of anti-ADAMTS13 antibodies. Similar to hemophilia with inhibitors, even high-dose replacement may not be able to overcome such inhibitors.…”

“…Following the phase I trial, 38 a phase III trial of rADAMTS13 (TAK-755) is underway (ClinicalTrials.gov identifier NCT04683003), in parallel with an expanded access program (ClinicalTrials.gov identifier NCT05770219) and first case reports of successful treatment of cTTP patients with rADAMTS13 have been published. 84 85 86 TAK-755 has been approved by the Food and Drug Administration (FDA) in November 2023 for the treatment of patients with congenital ADAMTS13 deficiency ( ), and approval in Europe can be expected soon. It will considerably ease the treatment burden for cTTP patients as home self-administration like in hemophilia will be possible as are higher ADAMTS13 trough levels, which will hopefully help reduce long-term morbidity and mortality in cTTP.…”

A British Society for Haematology Guideline: Diagnosis and management of thrombotic thrombocytopenic purpura and thrombotic microangiopathies

“…Proposed advantages include significantly higher ADAMTS13 levels and ease of administration compared to plasma infusion. [131][132][133] Recent data suggest patients may benefit from prophylaxis, since non-overt symptoms may represent subacute microvascular thrombi. The International cTTP Registry found 50% of cTTP patients at least 40 years of age not on prophylaxis had more than one arterial thromboembolic event, 123 whilst the UK Registry showed symptom resolution in 88% of the 24 patients commencing regular prophylaxis for headaches, lethargy and abdominal pain without laboratory evidence of TTP or end-organ damage.…”

“…Recombinant human ADAMTS13 is now in phase 3 clinical trial with phase 1 trials confirming safety and tolerability. Proposed advantages include significantly higher ADAMTS13 levels and ease of administration compared to plasma infusion 131‐133 …”

Caplacizumab: A game changer also in pregnancy‐associated immune‐mediated thrombotic thrombocytopenic purpura?

“…Importantly, the therapeutic arsenal of TTP should be soon expanded with the availability of a recombinant form of ADAMTS13 termed TAK755 9 . In this regard, the recent encouraging experience of a pregnant patient treated successfully with TAK755 for a congenital form of TTP insufficiently controlled with the usual standard of care consisting in plasma infusions 10 opens promising perspectives also for the management of pregnant women with the autoimmune form of the disease, as reaching strong levels of evidence is challenging in these patients who are usually excluded from clinical trials.…”