NovoEight (turoctocog alfa) / Novo Nordisk - LARVOL DELTA

Study for Turoctocog Alfa Treatment Regimen in Iraqi Haemophilia A Patients (clinicaltrials.gov) - P=N/A | N=900 | Recruiting | Sponsor: Novo Nordisk A/S | Trial completion date: May 2025 ➔ Aug 2025 | Trial primary completion date: May 2025 ➔ Aug 2025

Trial completion date • Trial primary completion date • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Comparative Efficacy of Recombinant FVIII and Recombinant FVII Biosimilars in Severe Hemophilia A. (PubMed, Clin Appl Thromb Hemost) - "The only possible treatment for this bleeding condition is factor concentrate.AimThe aim of this study is to compare the effect of recombinant factor VIII (rFVIII) and recombinant factor VII (rFVII) on prothrombin time (PT), activated partial thromboplastin time (aPTT), FVIII and FVII in severe HA.MethodologyA mixing study was conducted on 30 samples of severe HA patients to assess the correction of PT, aPTT, FVIII, and FVII values using biosimilars of rFVIII (NovoEight and Kogenate FS) and rFVII (NovoSeven and AryoSeven) using a fully automated coagulation analyser 'Ceveron alpha'.ResultsAll the four drugs demonstrated a significant alteration for both PT (P < .0001) and aPTT (P < .0001) values. Two different groups of biosimilars were found to have a high potential to alter the PT and aPTT values. The FVIII biosimilars are efficient in increasing the FVIII levels."

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

Study for Turoctocog Alfa Treatment Regimen in Iraqi Haemophilia A Patients (clinicaltrials.gov) - P=N/A | N=900 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2024 ➔ May 2025 | Trial primary completion date: Nov 2024 ➔ May 2025

Enrollment open • Trial completion date • Trial primary completion date • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

The Influence of Coagulation Factor Biosimilars in Shortening the Activated Partial Thromboplastin Time in Patients with Hemophilia a (ASH 2024) - "Negative correlation was observed between PT and FVII values after adding Kogenate FS (r=-0.103, p<0.001), aPTT and FVIII values after adding Kogenate FS (r=-0.898, p<0.001), aPTT and FVIII values after adding NovoEight (r=-0.865, p<0.001), as well as aPTT and FVIII values after adding AryoSeven (r=-0.647, p<0.001).Conclusion : All the investigated drugs significantly shorten aPTT values and increase values of FVIII and FVII. In terms of efficacy, no difference exists between AryoSeven and NovoSeven, as well as between Kogenate FS and NovoEight only in altering PT."

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

Study for Turoctocog Alfa Treatment Regimen in Iraqi Haemophilia A Patients (clinicaltrials.gov) - P=N/A | N=900 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New trial • Hematological Disorders • Hemophilia • Rare Diseases

Continuous Infusion of Turoctocog Alfa in Patients With Mild to Moderate Hemophilia A: A Case Series. (PubMed, Am J Ther) - No abstract available

Journal • Hematological Disorders • Hemophilia • Rare Diseases

Comparison of Coagulation Factor VIII Biosimilars (Kogenate FS Vs NovoEight) in Altering Prothrombin Time, activated Partial Thromboplastin Time, and levels of Factors VII and VIII in Hemophilia A (ISTH 2024) - "In a comparison of both of the investigational drugs to the original values of PT, aPTT and FVIII, among-group comparison with post-hoc pairwise comparisons showed a high statistically significant difference for aPTT and FVIII, compared to pre-treatment values (Table 1). A negative correlation was observed between PT and FVII values after adding Kogenate FS (r=-0.103, p< 0.001), aPTT and FVIII values after adding Kogenate FS (r=-0.898, p< 0.001), aPTT and FVIII values after adding NovoEight (r=-0.865, p< 0.001). Conclusion(s) : These investigated drugs significantly shorten aPTT values and increase values of FVIII and FVII."

Hematological Disorders • Hemophilia • Rare Diseases

Comparison of FVIII and concizumab in thrombin generation assays under different conditions (ISTH 2024) - "Under these conditions, FVIII (NovoEight, Novo Nordisk; 0.03–2.0 IU/mL) was compared with 4,000 ng/mL concizumab. The activity of FVIII increased with increasing FXIa concentrations, whereas the activity of concizumab was consistent under all conditions tested, independent of FXIa concentration (Figure 1). Consequently, the level of FVIII similar in activity to 4,000 ng/mL concizumab decreased as the FXIa concentration increased. In the absence of supplemented FXIa, the thrombin peak with 4,000 ng/mL concizumab corresponded to 0.9 IU/mL FVIII, and the endogenous thrombin potential (ETP) to 1.3 IU/mL FVIII."

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

Variability in combinations of APTT reagent and substrate plasma for a one-stage clotting assay to measure factor VIII products. (PubMed, Int J Lab Hematol) - "In addition to APTT reagents, variations in F8DPs used for OSAs can also affect FVIII:C results. F8DPs as well as the APTT reagent used for OSA should be chosen with caution, and laboratories should evaluate reagents for F8DPs as they currently do for APTT reagents, especially when lot changes occur."

Journal

Real-world long-term safety and effectiveness of turoctocog alfa in the treatment of haemophilia A in Japan: results from a multicentre, non-interventional, post-marketing study. (PubMed, Hematology) - "The effectiveness and safety profiles were comparable to those observed in other turoctocog alfa trials; effectiveness analysis and consumption were not affected by treatment regimens. Long-term use of turoctocog alfa therapy in clinical practice posed no newly identified safety issues and was effective for prophylaxis and treatment of bleeds in patients with haemophilia A in Japan."

Journal • P4 data • Real-world • Real-world evidence • Dermatology • Hematological Disorders • Hemophilia • Pruritus • Rare Diseases

Efficacy and safety of turoctocog alfa in patients with hemophilia A requiring surgical procedures: A multicentre retrospective study. (PubMed, Transfusion) - "The efficacy and safety of turoctocog alfa were confirmed for the management of surgery in patients with hemophilia A. No adverse events were observed and overall efficacy was good."

Journal • Retrospective data • Cardiovascular • Dermatology • Hematological Disorders • Hemophilia • Otorhinolaryngology • Rare Diseases • Urology

THIRd: Turoctocog Alfa in Haemophilic Italian Patients: Protection and Engagement in Recreational Activities (clinicaltrials.gov) - P=N/A | N=18 | Completed | Sponsor: Novo Nordisk A/S | Enrolling by invitation ➔ Completed | N=75 ➔ 18

Enrollment change • Trial completion • Hematological Disorders • Hemophilia • Rare Diseases

Mim8 interference on the measurement of FVIII Standard and Extended half-life products using selected FVIII Chromogenic Assays (ISTH 2023) - " Severe Hemophilia A plasma (HRF, Inc.) spiked with ADVATE®, Novoeight®, Esperoct® or ELOCTATE® to concentrations of 0.050, 0.100, 0.150, 0.200, and 1.000 IU/mL and Mim8 to 0, 3, 6 and 12 µg/mL, were used to investigate Mim8 interference. The bovine CSA showed no notable interference at all FVIII/Mim8 concentrations for all products (Fig 1). For the bovine/human CSA (Fig 2), FVIII levels ≤0.20 IU/mL, showed a Mim8 dose dependent interference increase with the largest fold increase (2.4 to 4.5, ADVATE®) at low FVIII levels (0.05 IU/mL). More interference by Mim8 was observed in SHL products."

Hematological Disorders • Hemophilia • Rare Diseases

Matching Adjusted Indirect Comparisons Between Personalized Prophylaxis with Simoctocog Alfa versus Standard Prophylaxis with Turoctocog Alfa in Adults with Severe Hemophilia A (ISTH 2023) - "After matching the two populations, the effective sample size (ESS) for simoctocog alfa was 43.1. The percentage of patients with zero bleeds was significantly higher with simoctocog alfa than turoctocog alfa (74.2% versus 28.6%) (Figure 1, Table 1). The total, spontaneous and joint annualized bleeding rates (ABRs) were significantly lower with simoctocog alfa (1.7, 1.0 and 0.9, respectively) than with turoctocog alfa (6.7, 4.6 and 5.2, respectively) (Table 1)."

Clinical • Hematological Disorders • Hemophilia • Rare Diseases

Area under the curve: Comparing the value of factor VIII replacement therapies in haemophilia A. (PubMed, Haemophilia) - "This analysis concludes that EHL products differ in relative AUC, have a larger AUC compared with standard half-life, and thus, different FVIII levels over time after infusion. This model may aid decision makers in the absence of head-to-head data."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

SERAPHINE: Safety and Efficacy in a ReAl-Life Study in Patients With Haemophilia Treated wIth NovoEight® for Surgery (clinicaltrials.gov) - P=N/A | N=60 | Completed | Sponsor: Nantes University Hospital | Recruiting ➔ Completed | N=100 ➔ 60 | Trial completion date: Apr 2022 ➔ Jun 2022 | Trial primary completion date: Apr 2022 ➔ Dec 2021

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Hematological Disorders • Hemophilia • Rare Diseases

Cost-Minimization Analysis of Damoctocog Alfa Pegol With the Treatment of Hemophilia A in Turkey (ISPOR-EU 2022) - "OBJECTIVES: To compare the lifetime consumption and cost of an extended-half liferecombinant factor VIII (rFVIII), the damoctocog alfa pegol, with reimbursed standard half life (SHL) factors (octocog alfa, moroctocog alfa, turoctocog alfa) for the treatment of haemophilia A (HemA) in patients with age ≥ 12 years in Turkey, from the public payer perspective. From the perspective of the public payer, damoctocog alfa pegol demonstrated good efficacy while being the lowest cost-generating option for the treatment of HemA patients in Turkey, when compared to existing reimbursed SHLs."

HEOR • Hematological Disorders • Hemophilia • Rare Diseases

A Cost Minimization Model of Afsteyela® (Lonoctocog-Alfa) for the Prophylactic Treatment of Pediatric Patients With Haemophilia A, in Mexico (ISPOR-EU 2022) - " A cost-minimization model (fo anual costs) was developed to estimate the treatment cost associated with lonoctocog-alfa, compared to turoctocog-alfa, moroctocog-alfa, octocog-alfa and simoctocog-alfa in pediatric patients with severe Haemophilia-A. For the treatment of patients with severe Haemophilia-A in Mexico, lonoctocog-alfa was a cost-saving option compared to existing rFVII in Mexico from the public payer perspective."

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

Methods for anti-factor VIII antibody levels in haemophilia A patients - validation of a multiplex immunoassay and comparability with assays measuring non-neutralising and neutralising antibodies (inhibitors). (PubMed, Haemophilia) - "The anti-FVIII antibody xFLI method is adaptable to clinical practice and more sensitive and reproducible than ELISA and CBA. Actual NNA titers are determined to both full-length and B-domain deleted FVIII. The xFLI is thus valuable for confirmation of all anti-FVIII antibodies."

Journal • Hematological Disorders • Hemophilia • Immunology • Rare Diseases

Performance of FVIII deficient plasma with VWF in the activity measurement of FVIII replacement products in plasma samples using an OSC assay. (ISTH 2022) - "Using acceptance criteria of 100 ± 25% recovery, 5 out of 6 products across all levels were assayed accurately. Mean FVIII% recoveries across all levels of Advate, Eloctate, Jivi, Novoeight and Wilate were 93, 95, 101, 113 and 95% respectively. The percent recoveries of Afstyla, after x2 conversion, fell within the acceptance criteria for levels of ≥ 0.1 IU/mL but over-estimated at 149.76% at the lowest level of 0.05 IU/mL."

Hematological Disorders • Hemophilia • Rare Diseases

Cost Minimization Analysis Evaluating Turoctocog ALFA (NOVOEIGHT®) and Product X As Prophylaxis Treatment for Paediatric and Adult Patients with Severe Haemophilia a in China (ISPOR 2022) - "Compared with product X, using Novoeight ® as prophylaxis treatment was likely to reduce the total annual costs both for prophylaxis and breakthrough bleeds treatment in paediatric and adult patients with severe haemophilia A in China."

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

Impact of Prophylactic Therapy on Health Related Quality of Life (HRQOL) of Children with Hemophilia a without Inhibitors: A Systematic Review and Meta-Regression Analysis (ISPOR 2022) - "The initial search yielded 2220 records. After title and abstract screening, 98 studies were retrieved for full text reading, of which 14 studies (778 patients from 12 countries) met the inclusion criteria for the meta-regression analysis. The proportion of patients on prophylactic treatment ranged from 0% to 100% of patients on a prophylactic regimen with regular administration of FVIII (11 studies), turoctocog alfa (two studies), or emicizumab (one study)."

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

POST-INFUSION MONITORING OF FVIII REPLACEMENT THERAPY – DATA FROM THE UK NEQAS BC EQA PROGRAMME 2021 (EAHAD 2022) - "WFH Guidelines for the laboratory measurement of Esperoct recommend both of these APTT reagents and chromogenic assays as suitable. The difference in measurement between assays for Esperoct would almost certainly be clinically relevant. No specific reagent recommendations are made for monitoring treatment with Novoeight."

Hematological Disorders • Hemophilia • Rare Diseases

AREA UNDER THE CURVE: INDIRECT PRODUCT COMPARISONS BETWEEN FACTOR VIII REPLACEMENT THERAPIES IN HAEMOPHILIA A (EAHAD 2022) - " The tool was created based on 11 identified crossover studies, presenting PK data for extended half-life (EHL) (Adynovi, Elocta, and Jivi) and standard half-life (SHL) products (Advate, Afstyla, Kogenate, Kovaltry, NovoEight, and ReFacto). Larger AUC for EHL compared to SHL products reflects higher FVIII over time after infusion, offering the option of longer injection intervals. In Scenarios 1 and 3, Jivi showed the largest AUC, and in Scenario 2, AUCs of EHLs Elocta and Adynovi were larger than Advate. This AUC tool may aid decision makers in comparing the relative value of FVIII concentrates in the absence of head-to-head trials."

Hematological Disorders • Hemophilia • Rare Diseases