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

ADAMTS13 variant (R1206K) exhibits increased VWF-cleaving activity and inhibition of thrombus formation under flow (ASH 2025) - "Our results demonstrate that we have identified a rADAMTS13 R1206K variant that exhibitsan enhanced enzymatic activity for cleaving a surrogate VWF peptide substrate and more physiologicalsubstrate such as multimeric VWF under static/denaturing and fluidic shear conditions. This rADAMTS13variant may be further explored for the treatment of TTP and other inflammatory thrombotic disordersassociated with relative deficiency of ADAMTS13 function."

Hematological Disorders • Thrombocytopenic Purpura • Thrombosis

Potential paradoxical hemostatic function of ADAMTS13 by enhancing collagen-induced platelet aggregation and activation (ASH 2025) - "Our findings revealed a novel but paradoxical function of rADAMTS13 promotinghemostasis while inhibiting thrombosis at the same time, like thrombin that has both prothrombotic andantithrombotic activities."

Cardiovascular • Hematological Disorders • Thrombocytopenic Purpura • Thrombosis • THBS2

Health state utility values in congenital thrombotic thrombocytopenic purpura (cTTP): A vignette-based valuation Study in the UK general population (ASH 2025) - "Vignette-based health states (HS) represented varying disease severities and treatments,including recombinant ADAMTS13 (rADAMTS13), plasma-based therapy (PBT) prophylaxis, and noprophylaxis...Several limitations should be noted: low scores even inasymptomatic states may reflect perceived long-term burden; and the online self-complete format mayhave limited participant understanding of treatment complexity. These values support the use of HRQoLin future evaluations of cTTP therapies."

Clinical • Hematological Disorders • Thrombocytopenic Purpura

Review of the management of patients with immune thrombotic thrombocytopenic purpura with persistently low adamts-13 activity - a challenge beyond rarity. (ASH 2025) - "7 patients were treated with caplacizumab and 1 with recombinantADAMTS13...Different immunosuppressive treatment combinations per patient: 2 patients: Corticosteroids+AntiCD201 patient: Corticosteroids+AntiCD20+Splenectomy4 patients: Corticosteroids+AntiCD20+Mycophenolate1 patient:Corticosteroids+AntiCD20+Mycophenolate+Daratumumab 1 patient: Corticosteroids+AntiCD20+Cyclosporine+Bortezomid1 patient: Corticosteroids+AntiCD20+Cyclosporine+Bortezomib+Splenectomy1 patient: Corticosteroids+Anti-CD20+Cyclosporine+Bortezomib+Mycophenolate.CONCLUSIONS - A small proportion of patients with iTTP don´t respond to first-line therapy and these individuals are athigh risk of relapse. A total of 11 patients meeting the specified criteria were identified, 7 women and 4 men. At diagnosis, the mean age was 43 years (range: 24–71). Laboratory parameters at presentation were:mean hemoglobin 9 g/dL (range: 6.5–12.7), mean platelet count 13.3 × 10³/mm³ (range: 5–22), and..."

Clinical • Review • Hematological Disorders • Thrombocytopenic Purpura • PROCR

Procedure-triggered late-onset congenital thrombotic thrombocytopenic purpura: Unmasking functional impact of a heterozygous synonymous ADAMTS13 variant (c.1716G>A) associated with reduced enzyme expression (ASH 2025) - "Congenital TTP should be considered in adult patients with recurrent thrombotic microangiopathy,especially when triggered by surgery or physiologic stress, and in the absence of a sustained inhibitorresponse. This case underscores the importance of recognizing the pathogenic potential of synonymousvariants and the need for expanded interpretation of ADAMTS13 genetic testing. Early recognition canprevent unnecessary PLEX and enable targeted therapy with plasma infusion or recombinant ADAMTS13.This case highlights a novel mechanism for late-onset cTTP and illustrates the serious implications ofdelayed diagnosis in adult patients."

Cardiovascular • Diabetes • Gastroenterology • Hematological Disorders • Hypertension • Immune Thrombocytopenic Purpura • Metabolic Disorders • Myocardial Infarction • Thrombocytopenia • Thrombocytopenic Purpura

Recombinant ADAMTS13 prophylaxis in patients with congenital thrombotic thrombocytopenic purpura: Final analysis from A phase 3 randomized, controlled study (ASH 2025) - P3 | "No new safety concerns were identified and, despite a smallsample size owing to the rarity of cTTP, participants reported greater treatment satisfaction duringrADAMTS13 prophylaxis compared with PBT. These findings support the clinical benefit of rADAMTS13prophylaxis in patients with cTTP."

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

A case series of pediatric patients with congenital thrombotic thrombocytopenia purpura (cTTP) treated with recombinant ADAMTS13 (ASH 2025) - "All three children in our case series, two of whom were switched from FFP, havetolerated rADAMTS13 without any reactions and have not experienced any TTP flares. Labparameters for all patients remain improved since starting treatment. Our data supports thesafety and efficacy of rADAMTS13 in young children."

Clinical • Cardiovascular • Hematological Disorders • Hepatology • Infectious Disease • Pediatrics • Respiratory Diseases • Thrombocytopenia • Thrombocytopenic Purpura

Clinical management of congenital thrombotic thrombocytopenic purpura in Latin America: Expert consensus from a modified Delphi panel (ASH 2025) - "Assuming equal access to all prophylaxis options, panelists indicatedthat recombinant ADAMTS13 would be the first-line prophylactic treatment over FFP and overcryoprecipitate-poor plasma (100% for all patient populations).Key considerations for cTTP patients in remission deciding whether to initiate prophylaxis includetolerability of treatment (11/11; 100%) and financial costs associated with treatment and regular hospitalvisits (11/11; 100%). Panelists confirmed a need for local guidelines specific to cTTP treatment andmanagement (13/13; 100%).ConclusionsOur findings offer important insights into current cTTP clinical management practices in LATAM, and aregenerally consistent with the latest ISTH guidelines published after the Delphi panel was conducted. Thisconsensus outlines essential factors influencing treatment choices and patient care, with considerationof regional particularities, and may help to guide LATAM physicians caring for patients with cTTP."

Clinical • Cardiovascular • Hematological Disorders • Thrombocytopenic Purpura • Thrombosis

Expert consensus on the clinical management of congenital thrombotic thrombocytopenic purpura in Asia-Pacific: A modified Delphi panel (ASH 2025) - "Current treatments for managing acuteTTP episodes and prophylaxis involve ADAMTS13 supplementation by infusion of fresh frozen plasma(FFP), solvent/detergent-treated FFP, intermediate-purity plasma-derived factor VIII (FVIII) concentrate,and more recently, recombinant ADAMTS13 (rADAMTS13).Although international guidelines on the management of thrombotic microangiopathy and/or TTPfrequently include sections on cTTP, there is limited up-to-date guidance specifically on the clinicalmanagement of cTTP...Panelists agreed that patients would be more likely toaccept prophylactic treatment if it could be self-administered at home rather than HCP-administered inclinicals/hospitals (11/11; 100%).ConclusionsOur findings provide valuable insights into current practices in APAC and are consistent with the latestISTH guidelines which were published after the Delphi panel concluded. This consensus may help toguide physicians caring for patients with cTTP in APAC, outlining key..."

Clinical • Cardiovascular • Hematological Disorders • Thrombocytopenic Purpura • Thrombosis

Modern Management of Congenital Thrombotic Thrombocytopenic Purpura (cTTP) (ASH 2025) - "Supported By C Dr Alice Taylor will outline current updates on treatment strategies in congenital TTP, illustrating the evolution of treatment options in congenital TTP in recent years, from plasma and plasma-derived products to recombinant ADAMTS13...Beyond this, Dr. Taylor will discuss how we need to examine what clinical outcomes we are targeting beyond prevention of acute TTP relapse."

Hematological Disorders • Thrombocytopenic Purpura

The Changing Landscape of the Care of Patients With Immune-Mediated and Congenital TTP (ASH 2025) - "Supported By C Thrombotic thrombocytopenic purpura (TTP), once almost universally fatal, is now a condition with markedly improved survival due to advancements in diagnostics, therapeutic plasma exchange, immunosuppressive therapies, and novel therapies like caplacizumab and recombinant ADAMTS13...He will discuss the integration of caplacizumab, corticosteroids, rituximab, and other emerging agents, including strategies to balance rapid disease control with long-term remission goals...Beyond this, Dr. Taylor will discuss how we need to examine what clinical outcomes we are targeting beyond prevention of acute TTP relapse."

Clinical • Cardiovascular • Cognitive Disorders • Hematological Disorders • Thrombocytopenic Purpura

Modern management of congenital thrombotic thrombocytopenic purpura (cTTP). (PubMed, Hematology Am Soc Hematol Educ Program) - "Treatment is based on ADAMTS13 replacement, previously limited to plasma and factor VIII concentrates and now expanded to recombinant ADAMTS13, which can achieve higher peak and trough levels with smaller volumes...We need further longitudinal data on how to optimize care. Key questions remain about prophylaxis and how to target optimal control of this condition through the alliance of improved treatment delivery and measures of clinical outcome."

Journal • Review • Cardiovascular • Hematological Disorders • Pain • Thrombocytopenic Purpura • Thrombosis

Quantitative System Pharmacology Modeling of the Effect of Recombinant ADAMTS13 on Platelets in Patients with Congenital Thrombotic Thrombocytopenic Purpura (ASH 2023) - P2, P3 | "This model-based virtual clinical trial simulation predicts that dosing with rADAMTS13 would provide >50% reduction in the HR of thrombocytopenia occurrences over PBT. Patients may also have a higher level of protection for 2-3 weeks when switching from rADAMTS13 to PBT. These findings supplement the assessment of clinical benefit of rADAMTS13 in the cTTP phase 3 study and show that increased ADAMTS13 activity following rADAMTS13 administration is likely to reduce occurrences of thrombocytopenia in cTTP."

Clinical • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis

Recombinant ADAMTS13 for the Treatment of Acute TTP Events in Patients with Congenital Thrombotic Thrombocytopenic Purpura: Results from the Phase 3 Randomized, Controlled, Crossover Study and the Phase 3b Continuation Study (ASH 2023) - P3 | "Conclusions The resolution of acute TTP events and an improvement in platelet count in patients with cTTP following treatment with rADAMTS13 was closely related to higher ADAMTS13 activity exposure. No serious TEAEs related to rADAMTS13 were reported."

Clinical • P3 data • Hematological Disorders • Pruritus • Thrombocytopenic Purpura • Thrombocytosis

Value of Prophylactic Plasma Treatment and Incidence of Acute Episodes in Patients Enrolled in the International Hereditary Thrombotic Thrombocytopenic Purpura Registry (ASH 2023) - "In this large hTTP patient cohort observed for five years on average, we confirm the incidence rate of acute events as reported by Tarasco et al. (Blood 2021; 137; 3563-75). Here, we demonstrate for the first time that hTTP patients with disease courses requiring prophylaxis benefit from this burdensome treatment, which was most evident in patients on long-term prophylaxis."

Clinical • Hematological Disorders • Thrombocytopenic Purpura

331. Thrombotic Microangiopathies/Thrombocytopenias and COVID-19-Related Thrombotic/Vascular Disorders: Clinical and Epidemiological: New Frontiers in TTP: Diagnostic and Therapeutic Innovations (ASH 2023) - "Oral abstracts in this session discuss population prevalence and recombinant ADAMTS13 for congenital TTP, provide insights into the kinetics of ADAMTS13 recovery in reponse to targeted therapies in immune TTP, and subclinical cardiac disease in immune TTP survivors."

Clinical • Heart Failure • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Thrombocytopenia

Sars-CoV2 ORF7a Protein Stimulates Synthesis and Secretion of Endothelial Von Willebrand Factor (ASH 2023) - "Our results demonstrate that ORF7a may upregulate VWF synthesis and secretion in endothelial cells, which enhances thrombus formation. Recombinant ADAMTS13 may rapidly remove endothelial surface ultra large VWF strings and exhibit therapeutic potential for COVID-19 associated thrombosis."

Cardiovascular • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Thrombosis

Proof-of-Concept in a Murine Model of Treatment of Thrombotic Thrombocytopenic Purpura Using Engineered Red Blood Cells Expressing Fragments of ADAMTS13 on Their Membrane (ASH 2023) - "A recombinant ADAMTS13 treatment for the congenital form is in advanced clinical trials but alternative treatment methodologies remain needed...The above data provide a proof-of-concept that RBCs expressing membrane-bound ADAMTS13 fusion proteins can be used as a therapeutic for congenital and acquired TTP. Experiments are in progress to determine in vivo, the TTP antibody resistance of these cells in the presence of anti-ADAMTS13 auto-antibodies from TTP patients."

Preclinical • Hematological Disorders • Thrombocytopenic Purpura

Population Pharmacokinetics and Exposure-Response Analyses to Demonstrate the Link of Causality between ADAMTS13 and the Clinical Effects of Recombinant ADAMTS13 Compared to Plasma-Based Therapies (ASH 2023) - P1, P3 | "Besides body-weight–based dosing, no additional dose adjustments of rADAMTS13 are needed in the cTTP patient population. A consistent and significant ADAMTS13 activity-response relationship was identified in which rADAMTS13 reduced the hazard of objective laboratory based TTP manifestations (thrombocytopenia and MAHA) in an activity-dependent manner. Overall, these findings suggest that rADAMTS13 at 40 IU/kg Q2W or Q1W offers a favorable prophylactic treatment effect over PBT that is attributable to higher ADAMTS13 activity."

Clinical • PK/PD data • Anemia • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura

Safety and Pharmacokinetics of Recombinant ADAMTS13 in Patients with Sickle Cell Disease: A Phase 1 Randomized, Double-Blind, Placebo-Controlled Study (ASH 2023) - P1 | "Despite the use of treatments such as hydroxyurea, many patients continue to experience VOCs. rADAMTS13 demonstrated a dose-proportional increase in ADAMTS13 antigen levels, which is consistent with linear PK. Findings from this study support the further investigation of rADAMTS13 as a potential therapeutic option for patients with SCD."

Clinical • P1 data • PK/PD data • Anemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

ADAMTS13 Protects Kidney Function in Alport Syndrome (KIDNEY WEEK 2025) - "In vivo, Col4a5-KO Alport mice were treated with bi-weekly administration of recombinant ADAMTS13 protein and kidney function was assessed...Conclusion Our findings reveal that endothelial metabolic dysfunction and ADAMTS13 downregulation contribute to microvascular injury and endothelial dysfunction in AS. These results suggest that ADAMTS13 restoration may serve as a promising therapeutic strategy to preserve endothelial function and slow CKD progression in AS, and potentially other forms of CKD."

Chronic Kidney Disease • Genetic Disorders • Metabolic Disorders • Renal Disease • COL4A5 • ICAM1 • VCAM1

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 • 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