Advate (octocog alfa) / Takeda - LARVOL DELTA

Long-term observational joint health study in patients initiating efanesoctocog alfa: baseline data (ISTH 2025) - P | "Prior prophylaxis (n=44) included efmoroctocog alfa (34%), emicizumab (24%), and octocog alfa (22%). Baseline AjBR and annualized bleed rates (ABRs) prior to starting efanesoctocog alfa are shown in Table 2; overall pre-switch ABR was >3. Table or Figure Upload"

Clinical • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Managing Hemophilia A in High-Risk Cardiac Procedures: A Left Atrial Appendage Closure Case Report (ISTH 2025) - "Methods The patient presents an extensive medical history,including atrial fibrillation,diabetes mellitus,hypertension,hepatitis C (treated with antiviral therapy),hemophilic arthropathy resulting from recurrent hemarthroses and a necrosis of the left lower extremity that necessitated finger amputation in 2023.This complex clinical profile underscored the critical need for comprehensive,multidisciplinary care.For the LAAC procedure,a meticulous factor VIII replacement protocol was implemented, beginning with the administration of 4000 IU of FVIII 2 hours prior to surgery.Perioperative FVIII levels were systematically measured to evaluate efficacy and inform subsequent prophylactic strategies.Postoperative management included dual antiplatelet therapy with aspirin and clopidogrel,complemented by a prophylactic FVIII regimen. Results Preoperative FVIII administration achieved a peak level of 121.4%.Postoperative monitoring showed a progressive decline in FVIII levels:72%..."

Case report • Clinical • Atrial Fibrillation • Cardiovascular • Diabetes • Hematological Disorders • Hemophilia • Hemophilia A • Hepatitis C • Hepatology • Hypertension • Infectious Disease • Inflammation • Metabolic Disorders • Osteoarthritis • Rare Diseases • Rheumatology

Impact of Extended Half-Life Factor VIII on Pharmacokinetics and Bleeding Rates in Hemophilia A (ISTH 2025) - "Patients initially treated with SHL FVIII (Beriate®, Immunate®, Octanate®, Advate®, Novoeight®, Hemophil M®, Xyntha®) and later switched to EHL FVIII (Adynovate®, Jivi®) were included. A weak, non-significant negative correlation existed between spontaneous bleeding and T1/2 for both SHL (r=-0.23, IC 95% -0.51 to 0.09, p>0.05) and EHL (r=-0.24, IC 95% -0.49 to 0.05, p>0.05). A significant positive correlation was observed between AUC and T1/2 (r=0.79, IC 95% 0.7 to 0.86, p<0.05) Table or Figure Upload"

PK/PD data • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

FVIII Half-Life Products: a Real-World Experience (ISTH 2025) - "Data on patient characteristics, treatment regimens, and pharmacokinetic profiles using WAPPS-Hemo (fig.1) , annual ABR and AJBR (table 1) were analyzed Results Among the FVIII products used, octocog alfa, efmoroctocog alfa, and damoctocog alfa showed median half-lives of 11.25 [10.75–12.25], 16.50 [13.75–17.75], and 15.38 [13.38–18.63] hours, respectively.Turoctocog alfa pegol exhibited the longest half-life at 19.75 [16.00–24.50] hours, enabling reduced infusion frequency. Bleeding control among the different FVIII-EHL was comparable. Table or Figure Upload"

Clinical • Real-world • Real-world evidence • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Analytical performance of an in-house von Willebrand factor-free FVIII inhibitor assay (ISTH 2025) - "ih-VWF-free: 1:1 full-length recombinant FVIII (rFVIII Advate®,Shire) and FVIII-VWF-deficient plasma (STA® deficient VIII)...Residual FVIII by One-stage assay (STA®C.K.Prest; STA®ImmunoDef VIII), Liatest®VWF:Ag, Diagnostica STAGO. Results Results are shown in Tables 1&2 Table or Figure Upload"

Effect of Mim8 and Emicizumab on Factor VIII Recovery by a Novel Bovine Chromogenic FVIII Assay (ISTH 2025) - "Methods Doses of Mim8 (0 to 20 µg/mL) and emicizumab (0 to 150 µg/mL) were spiked into plasma containing native or rFVIII (ADVATE®) at target 5, 20 and 100 % FVIII activity levels. Results Across all sample levels, Mim8 and emicizumab interference was observed using the human based assay. Both bovine chromogenic assays accurately measured native and rFVIII at ≥5 % FVIII in the presence of emicizumab or Mim8."

Thrombotic rates in bleeding disorder individuals treated with concentrate or bispecific antibody. (ISTH 2025) - "The thromboses in congenital haemophilia A included 37 myocardial infarctions, 26 venous thromboembolisms and 16 strokes. The rates of thrombosis were:Plasma FVIII/VWF 56/41,718 = 1.2/1000 patient yearsStandard recombinant FVIII 62/84,498 = 0.73/1000 patient yearsEHL recombinant FVIII 7/17,808 = 0.40/1000 patient years The rates for specific products (when used in all bleeding disorder patients) were:Advate 19/33,036 = 0.58/1000pyFEIBA 10/3,621 = 2.8/1000pyNovoSeven 17/6,954 = 2.4/1000pyEmicizumab 7/7,516 = 0.93/1000py"

Clinical • Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Myocardial Infarction • Rare Diseases • Venous Thromboembolism

Role of factor VIII as a regulator of angiogenesis and promoter of endothelial barrier stability (ISTH 2025) - "HA BOECs were treated in vitro with simoctocog alfa, efmoroctocog alfa, rurioctocog alfa pegol, damoctocog alfa pegol, octocog alfa, efanesoctocog alfa or non-factor therapy, emicizumab. Furthermore, simoctocog alfa in vivo rescue was greater compared to efmoroctocog alfa or efanesoctocog alfa. These effects on ECs may be mediated by the binding and signaling of simoctocog alfa to the ECs surface."

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Extended MAIC to Validate Results in Cases of Poor Population Overlap: An Application to Compare Prophylactic Treatments in Pediatric Patients With Hemophilia A (ISPOR 2025) - " Patient-level data from a single-arm trial evaluating a novel antihemophilic therapy (Int_A) were compared with aggregated data from the LEOPOLD Kids trial assessing octocog alfa (OctA)... The proposed method quantifies the risk of bias in MAIC when populations poorly overlap. By addressing imbalances and testing plausible scenarios, this approach enhances the robustness and credibility of MAIC results, reducing the risk of misleading conclusions."

Clinical • Hematological Disorders • Hemophilia • Hemophilia A • Pediatrics • Rare Diseases

A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=31 | Recruiting | Sponsor: Baxalta now part of Shire | Trial completion date: Jan 2025 ➔ Mar 2026 | Trial primary completion date: Jan 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Hemophilia

FVIII half-life products: A real-world experience. (PubMed, Thromb Res) - "EHL FVIII products offer significant clinical benefits, reducing the burden of frequent infusions and improving adherence while maintaining effective bleeding control. Despite these advancements, comprehensive evaluations of cost, safety, and long-term outcomes are essential to optimize their integration into haemophilia care."

Journal • Real-world evidence • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Assessing Different FVIII Doses and Frequencies in Immune Tolerance Induction (ITI) with ADVATE Among Hemophilia a Boys with Inhibitor (INITIATE Study) (clinicaltrials.gov) - P4 | N=110 | Recruiting | Sponsor: Runhui WU

New P4 trial • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Efficacy and Safety of Recombinant Factor VIII in Previously Untreated and Previously Treated Children with Hemophilia A: A Systematic Review. (PubMed, Adv Ther) - "Our analysis revealed that both octocog alfa and rurioctocog alfa pegol showed low inhibitor development, with octocog alfa having few treatment-related AEs. Regular monitoring for inhibitors during rFVIII therapy is important."

Journal • Review • Hematological Disorders • Hemophilia • Hemophilia A • Pediatrics • Rare Diseases

A Study of Recombinant Von Willebrand Factor (rVWF) in Pediatric and Adult Participants With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=38 | Completed | Sponsor: Baxalta now part of Shire | Active, not recruiting ➔ Completed

Trial completion • Hemophilia • Pediatrics

Effectiveness of PK-Guided Personalized Recombinant FVIII Treatment in Patients with Hemophilia A: Clinical Case Experiences Based on an Observational Study. (PubMed, J Blood Med) - "The results from this study in a small number of patients suggest that PK-guided regimen adjustment with myPKFiT may support optimization of the individual prophylactic administration of the FVIII products octocog alfa and rurioctocog alfa pegol. UMIN000044800."

Clinical • Journal • Observational data • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Role of Factor VIII As a Regulator of Angiogenesis and Promoter of Endothelial Barrier Stability (ASH 2024) - "HA BOECs were treated in vitro with the rFVIII products simoctocog alfa (Nuwiq®), efmoroctocog alfa (Elocta®), rurioctocog alfa pegol (Adynovate®), damoctocog alfa pegol (Jivi®), octocog alfa (Advate®), or emicizumab (Hemlibra®). Investigating the potential extra-coagulative role of FVIII could be crucial to understanding the key molecular targets at the cellular level which impair EC function in patients with HA. Knowledge of the possible effect of different rFVIII products and non-factor therapies on EC function can be used to optimize therapeutic approaches, which in turn may result in safer and more efficient treatment of HA."

Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Osteoarthritis • Rare Diseases

Cost Comparison of Efanesoctocog Alfa with Existing Factor VIII Replacement Therapies for Major Surgeries in People with Severe Hemophilia a (ASH 2024) - P2/3, P3 | "Objective To estimate total costs associated with perioperative hemostatic management in patients with severe HA treated with SHL (octocog alfa), EHL (rurioctocog alfa pegol and efmoroctocog alfa), and high-sustained (efanesoctocog alfa) FVIII replacement therapies. This is attributed to its high-sustained factor activity and reduced factor consumption during the reported perioperative period. The major limitations of the study were : the types of major surgeries varied among studies; the perioperative period data of octocog alfa were not found."

HEOR • Reimbursement • Surgery • US reimbursement • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Whole Genome Sequencing to Elucidate Genetic Modifiers of FVIII Clearance Heterogeneity in Patients with Hemophilia a (ASH 2024) - "Methods : In vivo clearance of rFVIII (Advate) was assessed in 49 adult patients with HA using MyPKFit...Crucially, this explained variance is expected to increase by our current efforts to include additional SNPs of interest derived from GWAS studies. Moreover, as illustrated for TC2N, these genomic strategies have high potential to identify novel pathways associated with FVIII and/or VWF clearance, thus being of direct translational relevance."

Clinical • Heterogeneity • Whole genome sequencing • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

A Study of Recombinant Von Willebrand Factor (rVWF) (TAK-577) in Children With Severe Von Willebrand Disease (vWD) (clinicaltrials.gov) - P3 | N=24 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting | Trial completion date: Feb 2027 ➔ Apr 2030 | Trial primary completion date: Feb 2027 ➔ Apr 2030

Enrollment open • Trial completion date • Trial primary completion date • Hemophilia

Efanesoctocog Alfa versus Standard and Extended Half-Life Factor VIII Prophylaxis in Adolescent and Adult Patients with Haemophilia A without Inhibitors. (PubMed, Adv Ther) - P3 | "Efanesoctocog alfa was associated with significantly lower ABRs (any, spontaneous and joint) compared with EHL or SHL prophylaxis therapies. Patients had, on average, 2.2 and 3.6 fewer bleeds per year versus EHL and SHL therapies, respectively."

Journal • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

A Study of Recombinant Von Willebrand Factor (rVWF) in Pediatric and Adult Participants With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=38 | Active, not recruiting | Sponsor: Baxalta now part of Shire | Recruiting ➔ Active, not recruiting | N=71 ➔ 38

Enrollment change • Enrollment closed • Hemophilia • Pediatrics

Evaluation of FVIII pharmacokinetic profiles in Korean hemophilia A patients assessed with myPKFiT: a retrospective chart review. (PubMed, Blood Res) - "This study confirmed significant interpatient variation in the PK of FVIII among Korean patients with hemophilia A. To achieve optimized prophylaxis, personalizing the regimen based on the PK profile of each individual patient is essential."

Journal • PK/PD data • Retrospective data • Review • Hematological Disorders • Hemophilia • Rare Diseases

Comprehensive laboratory assessment of lonoctocog alfa versus octocog alfa in severe haemophilia A. (PubMed, Haemophilia) - "Lonoctocog alfa and octocog alfa showed comparable recovery and safety in vivo as well as similar impacts on TG in vitro. Observed assay discrepancies on lonoctocog alfa demonstrated variability of results also between different FVIII CSAs."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

Damoctocog Alfa Pegol, a PEGylated B-domain Deleted Recombinant Extended Half-life Factor VIII for the Treatment of Hemophilia A: A Product Review. (PubMed, Drugs R D) - P1 | "The PK of damoctocog alfa pegol was shown to be improved as compared with that of sucrose-formulated rFVIII (rFVIII-FS, Kogenate®), and was also demonstrated to be non-inferior to and, for some variables, more favorable than rFVIII-Fc fusion protein, efmoroctocog alfa (Elocta®; NCT03364998), rurioctocog alfa pegol (BAX 855, Adynovate®/Adynovi®; NCT04015492), and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM, Advate®; NCT02483208). Efficacy for perioperative hemostasis has been demonstrated. Low bleeding rates were achieved across the studies, with twice weekly, every 5-day and every 7-day prophylaxis offering patients ≥ 12 years and their clinicians the chance to tailor treatment to individual needs and lifestyles, while maintaining long-term protection from bleeds and their consequences."

Journal • Review • Hematological Disorders • Hemophilia • Rare Diseases

INTRINSIC ACTIVATED THROMBIN GENERATION FOR EFFICACY AND MONITORING OF FACTOR VIII REPLACEMENTS AND MIMETICS (EHA 2024) - "Various extended half-life FVIII products and non-factor(mimetics) agents (such as emicizumab and fitusiran) were introduced as alternatives...TG was assessed by means of the CAT assay,optimized, and validated for the new PPP Reagent INT (contact activator, 4 µM phospholipids) for increasedsensitivity towards octocog alfa and/or emicizumab... Intrinsic activated thrombin generation may be used for efficacy and monitoring of different Hemophilia Areplacement therapies. Future applicability for this PPP Reagent INT assay in monitoring SHA patients has to bestudied in more detail."

Clinical • Hematological Disorders • Hemophilia • Rare Diseases