Advate (octocog alfa) / Takeda - LARVOL DELTA

Platelets stabilize factor VIIIa against loss of activity through subunit dissociation (ASH 2025) - "We wished to determine whether FVIII activity on platelet binding sites is enhanced bystabilization against A2 dissociation and/or protease cleavage.Like FVIII, the bispecific antibody emicizumab (Emi) serves as a cofactor that facilitates activation of FX byFIXa on either vesicles or platelets...Full-length recombinant factorVIII (octocog alfa (Antihemophilic Factor), Advate) was also used as a control (FVIII).Plasma clotting assays were performed using delipidated factor VIII-deficient plasma with corn trypsininhibitor to inhibit contact pathway activation...We are currently investigating the effect of the reported slower IIacleavage of full-length FVIII at residue 1689 as a possible explanation. Further experiments will probe therole(s) of FIXa and FX on decay of B domain deleted FVIII activity on platelets vs PLV.Our data shows that platelet binding sites provide enhanced factor VIII activity compared to phospholipidvesicles and suggests that stabilization of FVIIIa..."

A FXIa-modified clot waveform analysis for estimation of factor VIII level and emicizumab concentration in hemophilia A (ASH 2025) - "MethodsWe used plasma samples (N=42) from patients with severe hemophilia A (endogenous FVIII level <1IU/dL,without inhibitor) on treatment with emicizumab and spiked FVIII (standard half-life, octocog alfa) toachieve target levels (50-100 IU/dL). FXIa+TF-CWA and diluted aPTT+TF-CWA were better atdiscriminating additional FVIII in emicizumab samples than undiluted aPTT-CWA. These findings indicatethat FXIa+TF-CWA and diluted aPTT+TF-CWA better discriminate clotting dynamics of emicizumab andadditional FVIII substitution, which may be of use in clinical scenarios like peri-interventional monitoring."

Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Patient characteristics, treatment patterns, and bleeding in people with Hemophilia A without inhibitors initiating efanesoctocog alfa in the US: An administrative claims analysis (ASH 2025) - "The mean (SD) Charlson Comorbidity Index score among all patients was 0.49 (1.28).Within the 180-day pre-index period, 81.3% of patients received any prophylaxis (FVIII or emicizumab),5% used on-demand FVIII therapy only, and 13.7% patients were not treated with FVIII or emicizumab.The most commonly used products as on-demand or prophylactic prior to index were efmoroctocog alfa(30.0%), octocog alfa (17.5%), emicizumab (15.0%), and rurioctocog alfa pegol (11.3%). This retrospective claims analysis showed that bleed rates among PwHA receiving Efa werelow, consistent with outcomes observed in clinical trials. Most patients transitioning to Efa werepreviously treated with EHLs. Majority of patients continued treatment during the follow-up period, withrelatively low switching or discontinuation of treatment."

Clinical • Cardiovascular • Genetic Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Hypertension • Immunology • Obesity • Rare Diseases • Rheumatology

Cost-Savings Analysis of Fitusiran Prophylaxis: Reducing Breakthrough Bleeding Treatment Expenditure in the Kingdom of Saudi Arabia (ISPOR-EU 2025) - P3 | "For people with haemophilia (PwH) A without inhibitors, episodic treatments comprised octocog alfa, efmoroctocog alfa and rurioctocog alfa pegol for PwH A and nonacog alfa, albutrepenonacog alfa and eftrenonacog alfa for PwH B. Treatments included for PwH with inhibitors were factor VIII inhibitor bypassing activity (FEIBA) and eptacog alfa. In the KSA, fitusiran AT-DR prophylaxis may considerably reduce breakthrough bleed management costs in PwH versus CFC/BPA prophylaxis. Cost savings are predicted to be more substantial in PwH with inhibitors than in those without inhibitors."

HEOR • Hematological Disorders • Hemophilia • Rare Diseases

Cost-Savings Assessment of Fitusiran Prophylaxis in Minimizing Breakthrough Bleeding Treatment Expenses in the United Arab Emirates (ISPOR-EU 2025) - P3 | "The episodic treatments included were efmoroctocog alfa, octocog alfa and rurioctocog alfa pegol for people with haemophilia (PwH) A without inhibitors and albutrepenonacog alfa, nonacog alfa and eftrenonacog alfa for PwH B without inhibitors...A scenario analysis examined the impact of vial sharing. Among PwH without inhibitors, fitusiran AT-DR enabled per-bleed savings ranging from UAE Dirham (AED) 4,625 (efmoroctocog alfa) to AED 11,521 (rurioctocog alfa pegol) in PwH A and from AED 8,935 (nonacog alfa) to AED 30,053 (albutrepenonacog alfa) in PwH B. In PwH with inhibitors, fitusiran AT-DR usage generated per-bleed savings of AED 71,846 (FEIBA) to AED 90,761 (eptacog alfa). In the UAE, fitusiran AT-DR prophylaxis may considerably reduce costs associated with episodic treatments for breakthrough bleeds in PwH compared with CFC/BPA prophylaxis. PwH with inhibitors might have larger cost savings than those without inhibitors."

HEOR • Hematological Disorders • Hemophilia • Rare Diseases

Chronic Disease Outcomes As Predictors of Quality of Life in Patients with Hemophilia Α: Data from the Real-World AHEAD International Study (ASH 2023) - P | "The international Antihemophilic factor Hemophilia A outcome Database (AHEAD) study (NCT02078427) is an ongoing prospective, non-interventional, multicenter study evaluating the long-term safety and effectiveness of FVIII replacement in patients with HA receiving either octocog alfa or rurioctocog alfa pegol (ADVATE®; ADYNOVATE® [US] / ADYNOVI™ [Europe]; Baxalta US Inc. In this Mixed Effects Model, chronic pain level and number of PJs both had a statistically significant negative association with QoL, highlighting the importance of managing these chronic outcomes with effective treatment."

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

Successful Management of Intracranial Hemorrhage with Emicizumab in a Newborn with Severe Hemophilia a: A Case Report (ASH 2023) - "Neonate received tranexamic acid infusions 40 mg/kg die and 50 IU/Kg of intravenous recombinant factor VIII concentrate (octocog alfa). ConclusionsThe combined use of emicizumab and antifibrinolytics was successful in treating acute intracranial hemorrhage. To the best of our knowledge, this is the first pediatric case of successful management of intracranial hemorrhage with emicizumab in a newborn with severe HA."

Case report • Clinical • Cerebral Hemorrhage • CNS Disorders • Epilepsy • Hematological Disorders • Hemophilia • Hemophilia A • Pediatrics • Rare Diseases

Cost-Effectiveness of Emicizumab Vs Efanesoctocog Alfa, Standard Half Life (SHL) and Other Extended Half Life (EHL) FVIII Products for Prophylaxis in People with Severe Hemophilia a without Inhibitors (ASH 2023) - "Advate and Eloctate data were used to represent SHL and EHL, respectively. Findings in this cost-effectiveness analysis suggest that emicizumab is less costly and more effective (i.e., dominant) over a lifetime compared with available FVIII prophylaxis in pediatrics and adult PwHA in the US."

Cost effectiveness • HEOR • Hematological Disorders • Hemophilia • Hemophilia A • Pediatrics • 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

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

Preventing Bleeds in Pediatric Patients With Hemophilia A: Which Factor Replacement Therapy Offers the Best Protection and at What Cost? (ISPOR-EU 2025) - "Second lowest number of bleeds was achieved with efanesoctocog alfa (Altuviiio/Altuvoct) with 3.90 bleeds, following Efmoroctocog alfa (Elocta), turoctocog alfa pegol (Esperoct), turoctocog alfa (NovoEight), simoctocog alfa (Nuwiq), octocog alfa (Kovaltry), Afstyla (lonoctocog alfa) and octocog alfa (Advate) with 9.80, 9.85, 9.85, 11.85, 16.85, 18.45 and 18.75 bleeds, respectively. Prevention of bleeds is of utmost importance when treating pediatric patients with hemophilia A. Choosing a treatment with the lowest possible bleeding rates can support the physical development of the patient. This analysis showed that the lowest number of bleeds and lowest costs are estimated to be reached by damoctocog alfa pegol (Jivi)."

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

Analysis of Pooled Real-World Utilization and Outcomes Data of rVIII-Single Chain Compared With Standard and Extended Half-Life FVIII Products for Prophylaxis of Hemophilia A in France, Germany, and Italy (ISPOR-EU 2025) - "Prophylaxis with rVIII-SingleChain may reduce consumption and improve bleed protection compared with SHL FVIII products, and may provide comparable protection to EHL FVIII products."

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

Safety, Efficacy, and Pharmacokinetic Evaluation of rVWF in Chinese Subjects With von Willebrand Disease (ChiCTR) - P3 | N=20 | Not yet recruiting | Sponsor: The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

New P3 trial • Hemophilia

Clinical efficacy and safety of Octocog alfa in Chinese patients with hemophilia A: One-year follow-up results from the Antihemophilic Factor Hemophilia A Outcome Database (AHEAD) study (PubMed, Zhonghua Xue Ye Xue Za Zhi) - P | " Joint mobility improved in patients receiving either prophylactic or on-demand Octocog alfa. Bleeding episodes significantly reduced in patients receiving prophylactic treatment, particularly in pediatric patients and those with severe HA."

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

Canadian Clinical Experience on Switching From Standard Half-life Recombinant Factor VIII (rFVIII), Octocog Alfa, to Extended Half-life rFVIII, Damoctocog Alfa Pegol, in Persons With Haemophilia A ≥ 12 Years Followed in a Comprehensive Haemophilia Care Program in Canada. (PubMed, Haemophilia) - "This is a plain language summary on switching from the medicine octocog alfa to a new medicine damoctocog alfa pegol (BAY 94-9027, Jivi) for the treatment of haemophilia A in Canada."

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

A Study of Recombinant Von Willebrand Factor (rVWF) in Chinese Participants With Von Willebrand Disease (vWD) (clinicaltrials.gov) - P3 | N=20 | Not yet recruiting | Sponsor: Takeda

New P3 trial • Hemophilia

Effectiveness of Octocog Alfa (BAY 81-8973) to Treat People With Haemophilia A Enrolled in the ATHNdataset, Including Under-Represented Subgroups. (PubMed, Eur J Haematol) - "PwHA treated with octocog alfa in the ATHNdataset, including important subgroups, reported a low number of bleeds; thus, octocog alfa offers an effective therapeutic option."

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

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