Advate (octocog alfa) / Takeda - LARVOL DELTA

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

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) - "In this analysis, we apply a novel method to quantify the risk of bias when comparing samples with significantly different characteristics. 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

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

INDIVIDUAL PHARMACOKINETIC EVALUATION OF FIXED-SEQUENCE SINGLE-DOSE OCTOCOG ALFA, RURIOCTOCOG ALFA PEGOL, AND EFANESOCTOCOG ALFA IN ADULTS WITH SEVERE HEMOPHILIA A (EHA 2024) - P1 | "Consistent superiority regarding time over 40% FVIII activity, half-life, clearance, and FVIII exposure wereobserved with efanesoctocog alfa compared with SHL and EHL FVIII in all patients. No serious TEAEs orinhibitor development were reported for efanesoctocog alfa. Study funded by Sanofi and Sobi."

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

COMPARATIVE EVALUATION OF QUALITY OF LIFE IN HEMOPHILIA A PATIENTS UNDER PROPHYLAXIS: A 4-YEAR PERSPECTIVE (EHA 2024) - "Consequently, 20 patients previously under prophylaxis with standard half-life (SHL) products (INN-octocog alfa, octocog alfa, moroctocog alfa), transitioned to prophylactic treatment utilizing extended half-life(EHL) products (rurioctocog alfa pegol, efmoroctocog alfa, damoctocog alfa pegol), while 4 remained on SHL. A comprehensive analysis of 4 years' worth of data reveals a significant improvement across all quality-of-lifedimensions, underscoring the imperative for improved and personalized prophylactic interventions to achieveoptimal efficacy. Tailoring treatment regimens to align with the emotional and physical well-being of patientsholds promise for the implementation of more successful clinical approaches."

Clinical • HEOR • CNS Disorders • Depression • Hematological Disorders • Hemophilia • Pain • Psychiatry • Rare Diseases • Sexual Disorders

Intrinsic activated thrombin generation for efficacy and monitoring of emicizumab (ISTH 2024) - "Various extended half-life FVIII and non-factor products (such as emicizumab and Fitusiran) were introduced as alternatives... The TGA assay was optimized and validated for the new PPP Reagent INT (contact activator, 4 µM phospholipids) for measuring octocog alfa and emicizumab... TG in normal plasma triggered by PPP Reagent INT (36 replicates) was characterized by a lag time of 5.39±0.22 min, an endogenous thrombin potential (ETP) of 1451±38 nM.min, a peak height of 420±9 nM and a velocity index of 254±25 nM/min. The overall variability of the assay was < 10%(CV) for all parameters, with a within-run and between-day variation < 5%(CV). PPP Reagent INT failed to induce TG in plasmas deficient for FXII, FXI, FIX, or FVIII, whereas normal profiles were obtained for FVII deficient plasma."

Clinical • Hematological Disorders • Hemophilia • Rare Diseases

Factor VIII is a regulator of angiogenesis and a promoter of endothelial barrier stability (ISTH 2024) - "HA BOECs were treated in vitro with simoctocog alfa, efmoroctocog alfa, rurioctocog alfa pegol, damoctocog alfa pegol, or octocog alfa. Impaired tubulogenesis, migration and permeability of HA ECs vs healthy ECs were observed. A significant enhancement of EC functionality was demonstrated by treating HA BOECs with rFVIII products, with a higher positive effect for simoctocog alfa. Moreover, in NSG-HA mice treated with different rFVIII concentrates, and subsequently injected with Evans Blue dye, we showed a significant reduction of dye extravasation with a complete correction in mice treated with simoctocog alfa compared with other rFVIII products."

Hematological Disorders • Hemophilia • Rare Diseases

Physical activity engagement and health-related quality of life in patients with hemophilia A receiving either octocog alfa or rurioctocog alfa pegol versus other FVIII replacement therapies (ISTH 2024) - "The analysis included 500 patients (Table 1). Based on the ATE, patients in the treatment cohort were 16.4% (p < 0.01) more likely to engage in sport/activity compared with control (Table 2); however, no significant difference was observed between cohorts for the prophylaxis subgroup. No significant difference in EQ-5D index scores was observed between the treatment and control cohorts in either the total or prophylaxis subgroup (Table 2)."

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

Clinical outcomes in patients with hemophilia A receiving octocog alfa or rurioctocog alfa pegol versus other FVIII replacement therapies: Insights from the AHEAD, CHESS II, and CHESS PAEDs studies (ISTH 2024) - "The analysis included 1527 patients with 909 and 618 in the treatment and control cohorts, respectively (Table 1). For ABR, no statistically significant difference in ATE was observed between cohorts in the total or prophylaxis subgroup (Table 2). ATE showed a statistically significant (p < 0.01) difference of approximately -0.2 and -0.3 TJs for the treatment cohort compared with control in both the total and prophylaxis subgroup, respectively (Table 2)."

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

INDIVIDUAL PHARMACOKINETIC EVALUATION OF FIXED-SEQUENCE SINGLE-DOSE OCTOCOG ALFA, RURIOCTOCOG ALFA PEGOL, AND EFANESOCTOCOG ALFA IN ADULTS WITH SEVERE HEMOPHILIA A (THSNA 2024) - P1 | "No TEAEs were serious, led to treatment discontinuation, or were deemed related to efanesoctocog alfa treatment.ConclusionConsistent superiority regarding time over 40% FVIII activity, half-life, clearance, and FVIII exposure were observed with efanesoctocog alfa compared with SHL and EHL FVIII in all patients. No serious TEAEs or inhibitor development were reported for efanesoctocog alfa."

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

ACCURATE MEASUREMENT OF FACTOR VIII ACTIVITY AND INHIBITORS IN THE PRESENCE OF MIM8 (THSNA 2024) - " To assess FVIII activity of SHL and EHL products, severe HA plasma was spiked with ADVATE®, Novoeight®, Esperoct®, or ELOCTATE® (5, 10, 15, 20, and 100 IU/dL final concentrations) and Mim8 (0, 3, 6, and 12 µg/mL final concentrations). FVIII activity of SHL and EHL products was accurately measured in the presence of Mim8 using bovine CSAs. Using FVIII CSAs with bovine reagents, FVIII inhibitor levels up to approximately 5.0 BU were accurately measured in HA plasma in the presence of up to 40 µg/mL Mim8."

Hematological Disorders • Hemophilia • Rare Diseases