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

Long term follow-up outcomes in congenital thrombotic thrombocytopenic purpura. (PubMed, Blood) - "The majority of cTTP patients in the UK have now switched to recombinant ADAMTS13 (n=43, 58.9%), owing to inadequate symptom control (53.5%), plasma reactions (30.2%), or subclinical disease activity (16.3%). This work shows the breadth of ADAMTS13 genetic variants in cTTP, and demonstrates efficacy of regular prophylaxis in (i) reducing acute TTP episodes, and (ii) preventing end organ damage, but despite advances, cTTP related symptoms and the use of blood products, remained problematic."

Journal • Cardiovascular • CNS Disorders • Depression • Fatigue • Hematological Disorders • Mood Disorders • Pain • Psychiatry • Renal Disease • Thrombocytopenic Purpura

Kidney transplantation in congenital thrombotic thrombocytopaenic purpura: using recombinant ADAMTS13 to balance relapse and rejection. (PubMed, BMJ Case Rep) - "Finding an appropriate immunosuppressive regimen in cTTP transplant recipients can be challenging, as calcineurin inhibitors are associated with an increased risk of thrombotic microangiopathy (TMA), whereas prophylactic plasma exchange reduces the blood concentrations of mycophenolic acid and belatacept. Ultimately, he was treated with recombinant a disintegrin and metalloproteinase with a thrombospondin type one motif, member 13 (ADAMTS13) infusions, halting TMA and preventing future episodes. This is the first case of prophylaxis with recombinant ADAMTS13 in a kidney allograft recipient, illustrating its potential benefit over plasma exchange by assuring therapeutic immunosuppressants' concentrations and preventing both rejection and TMA-induced graft injury."

Journal • Hematological Disorders • Nephrology • Rare Diseases • Thrombocytopenic Purpura • Transplantation

Targeting hemostatic enzymes: from mechanistic insights to therapeutic frontiers. (PubMed, Curr Opin Hematol) - "Understanding hemostatic enzymatic regulation offers new avenues for risk stratification, diagnosis, and treatment of coagulation disorders. Although significant progress has been made, challenges remain in translating laboratory findings to clinical practice, necessitating further large-scale validation. Precision-guided enzymatic therapies hold promise for improving outcomes in acute care settings."

Journal • Cardiovascular • Hematological Disorders • Infectious Disease • Mood Disorders • Septic Shock

A microfluidic approach reveals ongoing disease activity in TTP patients despite clinical remission. (PubMed, J Thromb Haemost) - "We successfully used a flow-based assay to investigate VWF-dependent platelet recruitment as a rapid and sensitive monitoring tool for TTP patients, and an important research tool to study thrombogenesis. Our results using this assay, as a marker of ongoing microvascular thrombi formation, confirm the need to normalise ADAMTS13 activity levels in iTTP patients in clinical remission and the benefit of using recombinant ADAMTS13 in cTTP."

Journal • Hematological Disorders • Thrombocytopenic Purpura

Quantitative Systems Pharmacology Modeling of Platelet Responses to Recombinant ADAMTS13 in Patients With Congenital Thrombotic Thrombocytopenic Purpura. (PubMed, CPT Pharmacometrics Syst Pharmacol) - P3 | "These results provide confirmative evidence to support the use of rADAMTS13 in cTTP by integrating the current mechanistic understanding of interactions between ADAMTS13 and VWF multimers as its substrate, as well as key downstream parameters, primarily platelet count. Virtual patient clinical simulations from the QSP model supported the regulatory approval of rADAMTS13 in cTTP, highlighting the significant potential of QSP modeling to supplement clinical trial data in rare disease drug development."

Journal • Cardiovascular • Hematological Disorders • Rare Diseases • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis

Thrombotic thrombocytopenic purpura: early diagnosis and effective treatment in 2025. (PubMed, Intensive Care Med) - "The discovery of ADAMTS13 and its deficiency has led to breakthroughs in diagnosis and differential diagnoses, and the development of targeted treatments, including therapeutic plasma exchange, caplacizumab (an anti-VWF nanobody), and recombinant ADAMTS13. It also serves as a tribute to the collaborative efforts that have shaped our understanding of this disease over the past century. By raising awareness and sharing best practices, this educational initiative aims to further improve outcomes for patients with TTP and foster continued progress in the field."

Journal • Acute Kidney Injury • Cardiovascular • Critical care • Hematological Disorders • Nephrology • Renal Disease • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis

2025 focused update of the 2020 ISTH guidelines for management of thrombotic thrombocytopenic purpura. (PubMed, J Thromb Haemost) - "For patients with iTTP, no change to 2020's recommendations. For patients with cTTP, the panel supports ADAMTS-13 replacement. Where accessible, recombinant ADAMTS-13 provides the most favorable balance of benefits and risks. Otherwise, fresh frozen plasma may still be effective. Shared decision-making should include the benefits, the potential harms, and the burden of care."

Clinical guideline • Journal • Cardiovascular • Hematological Disorders • Thrombocytopenic Purpura • Thrombosis

The first report of rADAMTS13 concentrate usage in major surgery for a child with congenital TTP (ISTH 2025) - "Results The surgery was done successfully, and we did not observe any thrombotic or abnormal bleeding complication during surgery or post-operative period. The patient is on routine weekly rADAMTS13 prophylaxis after the surgery."

Clinical • Surgery • Cerebral Palsy • CNS Disorders • Developmental Disorders • Hepatology • Mental Retardation

Lessons from a case of recombinant ADAMTs13 therapy in pregnancy (ISTH 2025) - "Postop, she received rADAMTS13 40, 20, and 15 IU/kg on days 1, 2, and 3, respectively, followed by weekly 60 IU/kg for 12 weeks postpartum. Table or Figure Upload"

Clinical • Anemia • Cardiovascular • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis

Arginine methylation by protein arginine methyltransferase 1 (PRMT1) affects ADAMTS13 activity (ISTH 2025) - "Results We show that an inhibition of arginine methylation by a PRMTs inhibitor (MS023) in HEK293 cells expressing rADAMTS13 (Fig...Site-directed mutagenesis replacing 5 highly conserved methylation sites (R193, R498, R692, R1123, and R1206) led to identification of the critical role of R1206 in rADAMTS13 function. R1206K variant exhibited a 4~5 fold increased activity, likely resulting from conformational changes that abolished alloteric autoinhibition of ADAMTS13 function. Table or Figure Upload"

Cardiovascular • Hematological Disorders • Infectious Disease • Inflammation • Ischemic stroke • Mood Disorders • Novel Coronavirus Disease • Thrombocytopenic Purpura • PRMT1

A microfluidic ADAMTS13 test using miniaturized photons sensors for rapid near-patient testing. (ISTH 2025) - "Titration of recombinant ADAMTS13 (rADAMTS13) in ADAMTS13-deficient plasma was performed to verify sensitivity towards ADAMTS13 activity levels...The microfluidic ADAMTS13lum assay also detects reduced ADAMTS13 activity caused by inhibitory antibodies either added to normal plasma or dried-in on the microfluidic cartridge. Table or Figure Upload"

Clinical • Hematological Disorders • Thrombocytopenic Purpura

At-home recombinant ADAMTS13 prophylaxis: interim analysis from the phase 3b continuation study (ISTH 2025) - P3 | "For composite TTP manifestations, the mean±SD annualized event rate was 1.41±1.90. Table or Figure Upload"

P3 data • P3 data: top line • Fatigue • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Pediatrics • Thrombocytopenic Purpura

Innovative switch from plasma to recombinant ADAMTS13 in Japanese patients with congenital TTP (ISTH 2025) - "Patient feedback highlighted shorter administration times, reduced allergic reactions, and improved quality of life with rADAMTS13, though some expressed concerns about potential inhibitor development. Table or Figure Upload"

Clinical • Anemia • Hematological Disorders • Rare Diseases • Thrombocytopenia • Thrombocytopenic Purpura

Investigating the Mechanisms of ADAMTS13 Metalloprotease Domain Latency (ISTH 2025) - "Methods Recombinant ADAMTS13 activity was determined at increasing concentrations of DMSO, ethanol, acetonitrile, isopropanol, and ethylene glycol using FRETS-VWF73...However, ADAMTS13 cleaved the A2M bait region in the presence of 40% ethylene glycol or 12% DMSO. Functional inhibition of ADAMTS13 activity was not observed, likely due to instability of the inhibitor in the presence of organic solvents."

A2M

Therapeutic inhibitory effect of a novel humanized anti-ADAMTS13 antibody under high shear stress (ISTH 2025) - "Finally, the structural properties of recombinant ADAMTS13-D and A10 were analyzed using NMR and small-angle X-ray scattering (SAXS)...Furthermore, SAXS and docking simulations revealed the predicted structure of the ADAMTS13-D-A10 complex (Figure 2). Table or Figure Upload"

ADAMTS13 polymerization and interaction with its autoantibody fragment scFv4-16 by crosslink method (ISTH 2025) - "Methods Recombinant ADAMTS13 and its truncated MDTCS (first five N-terminal domains) were expressed in HEK293 cells and purified...However, scFv4-16 induced the formation of homo/heterodimers and multimers, indicated by multiple bands in PAGE, indicating complex interactions between the enzyme and ligand. Table or Figure Upload"

Hematological Disorders • Thrombocytopenic Purpura

Therapeutic effects of a novel humanized anti-GPIb-alpha Fab fragment in a murine model of TTP (ISTH 2025) - "Current treatment for immune TTP includes daily therapeutic plasma exchange (TPE), caplacizumab (anti-VWF nanobody), and immunosuppressives (such as corticosteroids and rituximab). Treatment for hereditary TTP includes frequent plasma infusion, or factor VIII concentrate, or recombinant ADAMTS13...More importantly, CA1001 appeared to be efficacious in preventing and/or treating a histone-induced “TTP-like” syndrome in Adamts13-/- mice, demonstrated by the alleviation of thrombocytopenia, prerenal injury, and formation of microvascular thrombosis in major organ tissues in the treated group compared with those in the vehicle controls. Table or Figure Upload"

Preclinical • Cardiovascular • Hematological Disorders • Inflammation • Ischemic stroke • Myocardial Infarction • Renal Disease • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis

Novel dual-action fusion proteins combining truncated ADAMTS13 and a nanobody against VWF (ISTH 2025) - "Possible treatments of TTP include recombinant ADAMTS13 or caplacizumab, which inhibits the GP1bα-VWF interaction. Both MDTCS-Syn-VWFA1 and MDTCS-RARAA-Syn-VWFA1 effectively inhibited ristocetin-activated VWF binding to platelets and prevented platelet agglutination, while ADAMTS13, MDTCS and MDTCS-RARAA had no effect. In the beads-on-a-string assay, all constructs showed dose-dependent reduction in the length and number of platelet stings on HUVECs, with MDTCS-RARAA-Syn-VWFA1 proving more effective than MDTCS-RARAA."

Hematological Disorders • Thrombocytopenic Purpura

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=33 | Active, not recruiting | Sponsor: Takeda | Trial completion date: Mar 2025 ➔ Jun 2026 | Trial primary completion date: Mar 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Hematological Disorders • Thrombocytopenic Purpura

Recombinant human ADAMTS13 attenuates LPS-induced acute kidney injury and renal microangiopathy in murine advanced liver fibrosis by cleaving vWF. (PubMed, Biochim Biophys Acta Mol Cell Res) - "Concomitantly, rADAMTS13 treatment promoted angiogenesis as well as inhibited vascular inflammation in the kidney of AKI-F mice. In conclusion, administration of rADAMTS13 may improve inflammation, oxidative stress, and reduced blood flow in liver and kidney tissues, thereby mitigating hepatorenal syndrome."

Journal • Preclinical • Acute Kidney Injury • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Nephrology • Renal Disease • KIM1 • LCN2 • SPP1

Use of PopPK and E-R Analyses toward Explaining Causal Link Between ADAMTS13 in Recombinant vs. Plasma-Based Therapies and Clinical Effects in cTTP. (PubMed, Clin Pharmacol Ther) - "Similar results were observed for protection against elevation of lactate dehydrogenase, a marker of microangiopathic hemolytic anemia. Overall, these results support the use of rADAMTS13 treatment for patients with cTTP."

Journal • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura

Advances in Research on the Release of von Willebrand Factor from Endothelial Cells through the Membrane Attack Complex C5b-9 in Sepsis. (PubMed, J Inflamm Res) - "Current therapeutic strategies targeting these pathways, including recombinant ADAMTS13 (rhADAMTS13), N-acetylcysteine (NAC), and complement inhibitors like eculizumab, face limitations in clinical translation, necessitating further validation of their efficacy. Additionally, investigating complement regulatory molecules such as CD59 may unlock novel therapeutic avenues. Deciphering the intricate interplay within the C5b-9-vWF axis and advancing precision therapies hold transformative potential for ameliorating sepsis outcomes."

Journal • Review • Hematological Disorders • Infectious Disease • Inflammation • Septic Shock • Thrombocytopenia • CD59 • NLRP3

Recombinant ADAMTS13 for Acute and Prophylactic Treatment of Congenital Thrombotic Thrombocytopenic Purpura in Pregnancy. (PubMed, J Thromb Haemost) - "Few studies have attempted to treat pregnant cTTP patients with rADAMTS13. We present a case of successful treatment with rADAMTS13 for an acute TTP exacerbation and maintenance during pregnancy in a cTTP patient with a history of pregnancy complications and an insufficient response to plasma infusions."

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

rADAMTS13 in cTTP: a new standard of care? (PubMed, Blood) - No abstract available

Journal

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