Advate (octocog alfa) / Takeda - LARVOL DELTA

Bleeding rates, healthcare utilization, and costs among patients with hemophilia a without inhibitors treated with concomitant octocog alfa or extended half-life factor VIII while on emicizumab prophylaxis. (PubMed, J Med Econ) - "Findings are limited by the retrospective design and reliance on claims data, which may omit home-treated bleeds, and misrepresent FVIII utilization due to billing complexities and assumptions about dispensed product use. While the choice of concomitant FVIII does not substantially influence ABRb or bleed-related HCRU, significantly lower pharmacy costs with octocog alfa compared with EHL agents highlight its potential cost saving and support its consideration as a preferred on-demand treatment option in patients with HA without inhibitors on emicizumab prophylaxis."

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

COST-MINIMIZATION ANALYSIS OF OCTOCOG ALFA VERSUS EMICIZUMAB PROPHYLAXIS IN PATIENTS WITH HEMOPHILIA A WITHOUT INHIBITORS IN CENTRAL AMERICA, ECUADOR AND PERÚ (ISPOR 2026) - "OBJECTIVES: To estimate annual treatment acquisition costs and conduct a cost minimization comparison of drug consumption between octocog alfa (Brand Kovaltry®) and emicizumab for prophylaxis in patients with hemophilia A without inhibitors in El Salvador, Panamá, Peru, Ecuador and Guatemala A cost minimization analysis was conducted from a payer perspective over one year, comparing dosing of octocog alfa to emicizumab for Year 1 and Year 2 separately. The cost minimization analysis indicates that octocog alfa is a cost-saving alternative, offering over 65% annual cost savings compared to emicizumab in El Salvador, Panamá, Peru and Guatemala and. In the case of Ecuador, offering over 50% annual cost savings compared to emicizumab"

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

Post Approval Observational Study to Learn More About How Safe Octocog Alfa is and How Well it Works in Patients With Severe Hemophilia A in India (clinicaltrials.gov) - P=N/A | N=33 | Not yet recruiting | Sponsor: Bayer

New trial • Real-world evidence • Hematological Disorders • Hemophilia • Hemophilia A • 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=39 | Recruiting | Sponsor: Baxalta now part of Shire | Trial primary completion date: Jul 2019 ➔ May 2020 | Trial completion date: Jul 2019 ➔ May 2020

Trial completion date • Trial primary completion date • Hemophilia

A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=39 | Recruiting | Sponsor: Baxalta now part of Shire | Not yet recruiting ➔ Recruiting | Initiation date: Nov 2016 ➔ Dec 2017

Enrollment open • Trial initiation date • Hemophilia

A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=39 | Not yet recruiting | Sponsor: Baxalta US Inc.

New P3 trial • Hemophilia

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

A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=34 | Recruiting | Sponsor: Baxalta now part of Shire | Trial completion date: Mar 2024 ➔ Jan 2025 | Trial primary completion date: Mar 2024 ➔ Jan 2025

Trial completion date • Trial primary completion date • Hemophilia

A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=34 | Recruiting | Sponsor: Baxalta now part of Shire | Trial completion date: Mar 2023 ➔ Mar 2024 | Trial primary completion date: Mar 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Hemophilia

A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=34 | Recruiting | Sponsor: Baxalta now part of Shire | Trial completion date: Dec 2022 ➔ Mar 2023 | Trial primary completion date: Jun 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Hemophilia

A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=34 | Recruiting | Sponsor: Baxalta now part of Shire | Trial completion date: Dec 2021 ➔ Dec 2022 | Trial primary completion date: Dec 2021 ➔ Jun 2022

Trial completion date • Trial primary completion date • Hemophilia

A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=39 | Recruiting | Sponsor: Baxalta now part of Shire | Active, not recruiting ➔ Recruiting

Enrollment open • Hemophilia

A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=39 | Active, not recruiting | Sponsor: Baxalta now part of Shire | N=24 ➔ 39 | Trial completion date: Jun 2020 ➔ Dec 2021 | Trial primary completion date: Jun 2020 ➔ Dec 2021

Enrollment change • Trial completion date • Trial primary completion date • Hemophilia

A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=24 | Active, not recruiting | Sponsor: Baxalta now part of Shire | Recruiting ➔ Active, not recruiting

Enrollment closed • Hemophilia

A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=24 | Recruiting | Sponsor: Baxalta now part of Shire | N=39 ➔ 24 | Trial completion date: Nov 2020 ➔ Jun 2020 | Trial primary completion date: Nov 2020 ➔ Jun 2020

Enrollment change • Trial completion date • Trial primary completion date • Hemophilia

A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD) (clinicaltrials.gov) - P3 | N=39 | Recruiting | Sponsor: Baxalta now part of Shire | Trial completion date: Jun 2020 ➔ Nov 2020 | Trial primary completion date: Jun 2020 ➔ Nov 2020

Trial completion date • Trial primary completion date • Hemophilia

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

Enrollment open • Hemophilia

Clinical Outcomes of Diluted Recombinant Factor VIII (Advate) for Continuous Infusion Use in Hemophilia A (ASHP 2025) - No abstract available

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

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