Trial reportDrug design, development and therapy2019
Increased branching and sialylation of N-linked glycans correlate with an improved pharmacokinetic profile for BAY 81-8973 compared with other full-length rFVIII products.
Trial report in Drug design, development and therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Population pharmacokinetic (PopPK) modelling indicates that patients switching to BAY 81-8973 from rFVIII-FS can continue their dosing schedule with improved protection.Haemophilia : the official journal of the World Federation of Hemophilia · 2020Trial
- PlasmaArteriosclerosis, thrombosis, and vascular biology · 2025Article
- Article
- Advances and challenges in plant N-glycoengineering: when fucosylation matters.Frontiers in plant science · 2025Review
- Molecular tag for promotingiScience · 2024Article
- Development of a Biosimilar of Agalsidase Beta for the Treatment of Fabry Disease: Preclinical Evaluation.Drugs in R&D · 2023Article
- Plasma Clearance of Coagulation Factor VIII and Extension of Its Half-Life for the Therapy of Hemophilia A: A Critical Review of the Current State of Research and Practice.International journal of molecular sciences · 2023Review
- Enhanced pharmacokinetics and reduced bleeds in boys with hemophilia A after switching to Kovaltry from other standard half-life factor VIII concentrates.Research and practice in thrombosis and haemostasis · 2022Article
- Real-world evidence on Kovaltry (81-8973) in children with moderate or severe hemophilia A in Europe: a nested cohort analysis.Orphanet journal of rare diseases · 2021Article
- Profiling, Relative Quantification, and Identification of Sialylated N-Linked Oligosaccharides by UPLC-FLR-ESI/MS After Derivatization with Fluorescent Anthranilamide.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Glycosylation of Therapeutic Proteins: A Critical Quality Attribute.Methods in molecular biology (Clifton, N.J.) · 2021Review
- BAY 81-8973 prophylaxis and pharmacokinetics in haemophilia A: Interim results from the TAURUS study.European journal of haematology · 2020Article
- Comparative glycosylation mapping of plasma-derived and recombinant human factor VIII.PloS one · 2020Article
- [Population pharmacokinetics of two recombinant human coagulation factor Ⅷ preparations in patients with hemophilia A].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBAY 81-8973 (Kovaltry) is an unmodified full-length recombinant factor VIII (rFVIII) for treatment of hemophilia A. The BAY 81-8973 manufacturing process results in a product of enhanced purity with a consistently high degree of branching and sialylation of N-linked glycans. This study evaluated whether a relationship exists between N-linked glycosylation patterns of BAY 81-8973 and two other rFVIII (sucrose-formulated rFVIII [rFVIII-FS; Kogenate FS]) and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM; Advate) and their pharmacokinetic (PK) characteristics. MATERIALS AND
methodsN-linked glycans or terminal carbohydrates were enzymatically removed from immobilized BAY 81-8973, rFVIII-FS, and rAHF-PFM proteins and analyzed using high-performance liquid chromatography to determine the percentage of individual N-linked glycan structures and degree of sialylation of each structure. PK data were available from two separate phase 1 crossover studies in which the PK profile of BAY 81-8973 was compared with that of rFVIII-FS (n=26) and rAHF-PFM (n=18) in patients with severe hemophilia A who received a single 50 IU/kg dose of each product.
resultsBAY 81-8973 and rFVIII-FS had increased N-linked glycan branching with higher levels of sialylation compared with rAHF-PFM. Levels of trisialylated glycans were 29.0% for BAY 81-8973 vs 11.5% for rFVIII-FS and 4.8%-5.5% for rAHF-PFM; tetrasialylated glycans were 12.0% vs 2.8% and 0.6%, respectively. Degree of sialylation was 96% for BAY 81-8973, 94% for rFVIII-FS, and 78%-81% for rAHF-PFM. Based on chromogenic assay results from the single-dose phase 1 PK studies, BAY 81-8973 half-life was 15% longer than that for rFVIII-FS and 16% longer than rAHF-PFM.
conclusionIncreased N-glycan branching and sialylation were seen for BAY 81-8973 vs rFVIII-FS and rAHF-PFM. Improved PK for BAY 81-8973 relative to rFVIII-FS and rAHF-PFM as seen in single-dose crossover PK studies might be related to this greater level of branching and sialylation, which can prolong the time BAY 81-8973 remains in the circulation.
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