Adzynma (apadamtase alfa /cinaxadamtase alfa) / Takeda, Meiji Seika - LARVOL DELTA

MHRA approves first UK treatment for congenital thrombotic thrombocytopenic purpura (cTTP) (GOV.UK) - "The Medicines and Healthcare products Regulatory Agency (MHRA) has today (12 May 2025) approved rADAMTS13 (ADZYNMA), the first UK treatment to treat congenital thrombotic thrombocytopenic purpura (CTTP) in patients of all ages...This medicine has been approved through the International Recognition Procedure (IRP). The IRP allows the MHRA to take into account the expertise and decision-making of trusted regulatory partners for the benefit of UK patients."

MHRA approval • Thrombocytopenic Purpura

Recombinant ADAMTS13 attenuates LPS-induced acute kidney injury and renal microangiopathy in mice with liver cirrhosis by cleaving vWF (EASL 2025) - "Administration of rADAMTS13 may improve inflammation, oxidative stress, and reduced blood flow in liver and kidney, thereby mitigating HRS."

Preclinical • Acute Kidney Injury • Fibrosis • Gastroenterology • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Nephrology • Renal Disease • ICAM1 • KIM1 • SELP • SPP1 • VCAM1

Development of a protease-resistant ADAMTS13 to improve stability against proteolytic degradation. (PubMed, Blood Adv) - "Recombinant ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was recently approved by the FDA for the treatment of heritable thrombotic thrombocytopenic purpura (TTP), and preclinical studies have demonstrated its efficacy in treating other thrombotic conditions...This work identifies prominent protease cleavage sites within ADAMTS13 and demonstrates that disruption of these sites does not impair its capacity to regulate VWF. Future work will explore the therapeutic efficacy of protease-resistant ADAMTS13 in vivo."

Journal • Hematological Disorders • Thrombocytopenic Purpura • ELANE

Therapeutic switch from plasma to recombinant ADAMTS13 for patients with congenital TTP from Japanese real-world data. (PubMed, Blood) - "Patients reported no allergic reactions after rADAMTS13 administration and appreciated the convenience of a single infusion of rADAMTS13, suggesting that rADAMTS13 is a safe and effective alternative to FFP in patients with cTTP. This is the first publication of patients with cTTP who switched FFP to novel rADAMTS13 from Japanese real-world-data."

Journal • Real-world evidence • Allergy • Chronic Kidney Disease • Hematological Disorders • Nephrology • Rare Diseases • Renal Disease • Thrombocytopenia • Thrombocytopenic Purpura

Prophylactic use of recombinant ADAMTS-13 during pregnancy for congenital thrombotic thrombocytopenic purpura. (PubMed, Res Pract Thromb Haemost) - "No anti-ADAMTS-13 antibodies developed. Prophylactic use of rADAMTS-13 during pregnancy may prevent relapse of cTTP and reduce the risk of fetal loss, but an optimal regimen requires further attention."

Journal • Hematological Disorders • Thrombocytopenic Purpura

Preventitive and therapeutic effects of a novel humanized anti-GPIbα Fab fragment in a murine model of thrombotic thrombocytopenic purpura. (PubMed, J Thromb Haemost) - "CA1001 can effectively inhibit VWF-platelet interaction and thrombus formation under various (patho)physiological conditions. Thus, CA1001 may be a potential candidate for further development as a novel therapeutic for immune-mediated and hereditary TTP and perhaps for other inflammatory thrombotic disorders such as ischemic stroke."

Journal • Preclinical • Cardiovascular • Hematological Disorders • Ischemic stroke • Renal Disease • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis

Arginine Methylation by PRMT1 Affects ADAMTS13 Secretion and Enzymatic Activity. (PubMed, Arterioscler Thromb Vasc Biol) - "An inhibition of arginine methylation by a PRMT inhibitor (a type I methyl transferase inhibitor, MS023) in human embryonic kidney 293 cells expressing recombinant ADAMTS13 and mice results in a significant reduction of ADAMTS13 secretion, but the secreted ADAMTS13 shows an increased specific activity; conversely, overexpression of PRMT1 in human embryonic kidney 293 cells and mice results in an increase of ADAMTS13 secretion, but the secreted ADAMTS13 exhibits a significantly reduced proteolytic activity...Site-directed mutagenesis of 5 highly conserved methylation sites (R193, R498, R692, R1123, and R1206) identifies the critical role of R1206 in ADAMTS13 function...These results demonstrate the crucial role of arginine methylation on ADAMTS13 secretion and activity. Our findings may shed new light on the mechanism of allosteric regulation of ADAMTS13, which may have a therapeutic implication."

Journal • Cardiovascular • Hematological Disorders • Thrombocytopenic Purpura • Thrombosis • PRMT1

Impact of new medications on the treatment of Immune TTP. (PubMed, Blood) - "The last decade has seen the introduction of two new licensed therapies for thrombotic thrombocytopenic purpura (TTP)-caplacizumab and recombinant ADAMTS 13 (rADAMTS 13), for immune (iTTP) and congenital TTP (cTTP) respectively. Future pathways need to replace plasma exchange in acute TTP and optimise/personalise rADAMTS 13 in cTTP. Future emphasis should focus on additional monoclonals/treatments to tackle ADAMTS 13 antibodies."

Journal • Hematological Disorders • Thrombocytopenic Purpura

ADAMTS13 Improves Endothelial Function and Reduces Inflammation in Diabetic Retinopathy. (PubMed, Cells) - "We study the protection against diabetes-induced retinal injury in experimental rats by supplementation with recombinant ADAMTS13...In HRMECs, ADAMTS13 attenuates the shedding of the soluble VE-cadherin and soluble syndecan-1 and the levels of phospho-ERK1/2, MCP-1, fractalkine, and ROS induced by diabetic mimetic conditions, the upregulation of ICAM-1 and VCAM-1 elicited by TNF-α, the adherence of monocytes induced by TNF-α, and VEGF-induced migration of human retinal microvascular endothelial cells. Our findings suggest that enhancing ADAMTS13 levels in situ ameliorates diabetes-induced retinal inflammation and vascular dysfunction."

Journal • Cardiovascular • Diabetic Retinopathy • Hematological Disorders • Inflammation • Metabolic Disorders • Ocular Inflammation • Retinal Disorders • Thrombosis • CDH5 • CTNNB1 • CX3CL1 • HMGB1 • ICAM1 • ITGA2B • MAPK1 • MAPK3 • MMP9 • SDC1 • TNFA • VCAM1

Injury induced endotheliopathy: overview, diagnosis, and management. (PubMed, Curr Opin Crit Care) - "Injury-induced endotheliopathy represents an important pathologic response to trauma. Key biomarkers, such as syndecan-1, can aid in the diagnosis, but testing is not yet available clinically. As the mechanisms of endotheliopathy are better understood, therapeutics are being identified and show promise. To date, plasma has been the most widely studied; however, like all therapeutics for injury-induced endotheliopathy, it has primarily been studied in the preclinical setting."

Journal • SDC1

ADAMTS13 Improves Hepatic Platelet Accumulation in Pyrrolizidine Alkaloids-induced Liver Injury. (PubMed, J Clin Transl Hepatol) - "Systemic administration of recombinant ADAMTS13 decreased hepatic platelet accumulation, downregulated VWF expression, and mitigated mouse hepatic necrosis. Hepatic platelet accumulation in PA-ILI was confirmed in both patients and mice. Deficiency of ADAMTS13 plays a critical role in platelet accumulation in PA-ILI, suggesting that ADAMTS13 could be a potential therapeutic target for this condition."

Journal • Hepatology • Liver Failure

A Mutant Complement Factor H (W1183R) Enhances Proteolytic Cleavage of von Willebrand Factor by ADAMTS13 Under Shear. (PubMed, J Thromb Haemost) - "These results demonstrate for the first time that W1183R-CFH but not WT-CFH protein enhances the proteolytic cleavage of VWF by ADAMTS13 under shear. This may be achieved by mechanic-induced conformational changes of the central A2 domain, leading to an altered cleavage of Tyr1605-Met1606 bond by ADAMTS13 under pathophysiological conditions."

Journal • Atypical Hemolytic Uremic Syndrome • Nephrology • CFH

Platelet Factor 4 (PF4) Binding to Neutrophil Extracellular Traps (NETs) and Von Willebrand Factor (vWF) Improves Bacterial Capture and Killing in an Electrostatic Charge-Dependent Manner (ASH 2024) - "vWF-coated channels were prepared by incubating channels with recombinant vWF (Vonvendi, 50µg/ml) after which they were subjected to flow at 20 dynes/cm2 to promote physiologic factor multimerization...Experiments were repeated with live green fluorescent protein (GFP) expressing E coli strains, including K12 E coli and the colistin-resistant PmrA53 E coli mutant that has reduced negative surface charge. To assess the effect of PF4 on bacterial-retention, NET-lined channels were infused with DNase I (Biolegend) and VWF-channels were infused with recombinant ADAMTS13 (Abcam) and N-acetylcysteine (NAC, Sigma-Aldrich)...PF4 also tethers bacteria to vWF, and while this does not directly promote bacterial killing, it may accelerate bacterial clearance. These results suggest that treatment with PF4 may act synergistically with antibiotics to improve bacterial clearance, with the most pronounced benefit potentially in thrombocytopenic patients."

Hematological Disorders • Infectious Disease • Septic Shock • Thrombocytopenia

Pharmacodynamic Activity of Recombinant ADAMTS13 Versus Plasma-Based Therapies in Congenital Thrombotic Thrombocytopenic Purpura: Interim Results of a Phase 3 Randomized, Controlled, Open-Label Study (ASH 2024) - P3 | "More patients receiving rADAMTS13 showed detectable ADAMTS13-mediated VWF cleavage products than with PBT at early timepoints, peaking immediately following PK-I treatment (1h postinfusion : rADAMTS13, 97% [34/35], PBT, 61% [22/36]; 24h : rADAMTS13, 69% [24/35], PBT, 47% [17/36]). Conclusions : These pharmacodynamic findings suggest that treatment with rADAMTS13, when compared with PBT, may provide a greater and more sustained reduction in VWF activity, further supporting the pharmacodynamic benefit of treatment with rADAMTS13 in patients with cTTP."

Clinical • P3 data • P3 data: top line • PK/PD data • Hematological Disorders • Thrombocytopenic Purpura

The Quest for Effective and Well-Tolerated Treatment for Congenital TTP: Half a Century of Experience in the United Kingdom (ASH 2024) - "These data highlight the need for a therapy with good tolerability and high efficacy, and which does not require hospital administration. We must review real-world data on rADAMTS13 and assess its ability to address this need."

Cardiovascular • Fatigue • Genetic Disorders • Hematological Disorders • Mood Disorders • Pain • Psychiatry • Thrombocytopenic Purpura • Thrombosis

Mutation Analysis of the ADAMTS13 Gene in Patients with Congenital Thrombotic Thrombocytopenic Purpura from the rADAMTS13 Phase 3 Study (ASH 2024) - P3 | "Conclusions : This analysis contributes to the genetic epidemiology of cTTP, with 7 novel pathogenic mutations identified, and one mutation described as frequent for the first time in patients with cTTP. Further analyses may uncover genotype-phenotype correlations."

Biomarker • Clinical • P3 data • Hematological Disorders • Thrombocytopenic Purpura

Uncovering Root Causes Underlying Gaps in the Evaluation and Integration of the Latest Clinical Evidence in Congenital Thrombotic Thrombocytopenic Purpura: Key Findings from a National Hematology Care Team Survey (ASH 2024) - "HCP knowledge of emerging evidence regarding new rADAMTS13 therapy was low, with only 26% identifying accurate information from the pivotal phase 3 281102 clinical trial...To optimize cTTP care, educational programming focused on integrating new clinical evidence for diagnosis and management of cTTP, including adoption of new therapies, and improving patient engagement strategies is critical. These insights can guide future initiatives to bridge persistent gaps in quality cTTP care."

Clinical • Hematological Disorders • Thrombocytopenic Purpura

Recombinant ADAMTS13 Prophylaxis in Pediatric Patients with Congenital Thrombotic Thrombocytopenic Purpura: Results from the Phase 3 Randomized, Crossover Study and the Phase 3b Continuation Study (ASH 2024) - P3 | "No dose adjustments were needed for pediatric patients. No new safety concerns with rADAMTS13 prophylaxis were identified."

Clinical • P3 data • Cardiovascular • Hematological Disorders • Infectious Disease • Pediatrics • Thrombocytopenia • Thrombocytopenic Purpura

Real-World Safety and Efficacy of rADAMTS13 in the Treatment of Congenital Thrombotic Thrombocytopenic Purpura in Pediatric Patients in Poland. (PubMed, J Thromb Haemost) - "Treatment with rADAMTS13 resulted in the normalization of laboratory parameters in all pediatric patients with cTTP."

Journal • Real-world • Real-world evidence • Allergy • Hematological Disorders • Pediatrics • Thrombocytopenic Purpura

Management of congenital thrombotic thrombocytopenic purpura in the era of recombinant ADAMTS13 protein: Recommendations from the Reference Center for Thrombotic Microangiopathies (CNR-MAT) (PubMed, Rev Med Interne) - "The rhADAMTS13 protein, intravenous infusion used for prophylaxis or on-demand, has been granted early access or compassionate use in cTTP in France in 2024. The objective of this document is to establish academic recommendations for the use of rhADAMTS13 in cTTP."

Journal • Review • Cardiovascular • Hematological Disorders • Obstetrics • Rare Diseases • Thrombocytopenic Purpura

100 years thrombotic thrombocytopenic purpura (TTP) - lessons learned? (PubMed, Dtsch Med Wochenschr) - "Two randomized controlled studies demonstrated the benefit of the selective bivalent anti-von-Willebrand factor (vWF) nanobody Caplacizumab, approved in 2019, in the treatment of iTTP. Modern therapeutic options include strategies for preemptive therapy for ADAMTS13-relapse as well as plasma exchange-free treatment. The use of recombinant ADAMTS13 may also expand the therapeutic options in iTTP patients in the future."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Thrombocytopenic Purpura • Thrombosis

A Multi-Criteria Decision Analysis (MCDA) to Determine the Value of Recombinant ADAMTS3 Vs Standard of Care in Congenital Thrombotic Thrombocytopenic Purpura (cTTP) in Spain (ISPOR-EU 2024) - "cTTP is recognized as a severe disease for which there are important unmet needs. Under this methodology, rADAMTS13 is perceived as a more effective, safer and more convenient therapeutic option than standard of care."

Hematological Disorders • Rare Diseases • Thrombocytopenic Purpura • Thrombosis • ADAMTS3

A Study of TAK-755 (rADAMTS13) With Little to No Plasma Exchange (PEX) Treatment in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP) (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: Takeda | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Disorders • Thrombocytopenic Purpura

The Highs and Lows of ADAMTS13 Activity. (PubMed, J Clin Med) - "In this article, we discuss the effects of low ADAMTS13 activity in congenital and immune-mediated TTP patients not only at presentation but once in a clinical remission. Evidence is emerging of the clinical effects of low ADAMTS13 activity in other disease areas outside of TTP, and here, we explore the wider impact of low ADAMTS13 activity on the vascular endothelium and the potential for recombinant ADAMTS13 therapy in other thrombotic disease states."

Journal • Review • Hematological Disorders • Thrombocytopenic Purpura • Thrombosis

In a nutshell: TTP and pregnancy. (PubMed, Br J Haematol) - "There may be a role, however, for newer therapies, including caplacizumab and recombinant ADAMTS13. Differentiation of immune TTP and congenital TTP is vital, particularly to guide the management of subsequent pregnancies."

Journal • Review • Hematological Disorders • Thrombocytopenic Purpura