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Extended Half-Life of the Double-Chain Recombinant Factor VIII-Fc Fusion Protein (FRSW107) in Previous Treated Hemophilia A Patients

1Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China, 2Jinan Central Hospital Affiliated to Shandong University, Jinan, China, 3Nanfang Hospital, Southern Medical University, Guangzhou, China, 4Shandong Blood Center, Jinan, China, 5Beijing Furen Ruihui Biomedical Research Institute Co., Ltd, Beijing, China

Abstract Number: PB0890

Meeting: ISTH 2020 Congress

Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical

Background: Fusion of Fc part of IgG to another protein is commonly used to extend the half- life of fused protein. Here we introduce a double- chain recombinant FVIII Fc fusion protein exhibit extended in vivo half- lives.

Aims: To determine the pharmacokinetics (PK), safety and tolerability of double chain recombinant human FVIII-Fc fusion protein (FRSW107) in previously treated patients (PTPs) with age >12 in a phase I clinical trial (clinicaltrials.gov: NCT03747653) which was approved by ethical committee of Hospital of Blood Diseases, CAMS&PUMC. .

Methods: PTPs (12 to 60 years old) with FVIII:C＜2% and without history of FVIII inhibitors were enrolled and received a single dose injection of rFVIII (Advate) at either 25 or 65 IU/kg followed by an equal dose of FRSW107. Blood samples for coagulation analysis were collected at scheduled time- points up to 240h after administration of FRSW107. Adverse events were recorded from obtaining of ICF to 28 days post administration of FRSW107. All subjects must sign the Informed Consent Form before screening.

Results: Seven subjects were enrolled in 25IU/kg group of FRSW107 and completed the ending visit. Seven subjects were enrolled in 65IU/kg group of FRSW107 and six completed the ending visit to date. Table1 shows the PK parameters of FRSW107. The Half-lives of FRSW107 are 20.2h and 22.98h derived from 25IU/kg and 65IU/kg cohort respectively, nearly 1.57 times of Advate. All adverse events were unrelated to study drug. None of the study subjects developed FVIII inhibitors.

Cohort 25IU/kg Cohort n=7 65IU/kg cohort (n=6)
Pharmacokinetics Control(Advate) Mean Trial(FRSW107) Mean Ratio(T/R)(%) Control(Advate) Mean Trial(FRSW107) Mean Ratio(T/R)(%)
Cmax(IU/dL) 68.41 53.4 78.05 134.36 95.17 70.83
λz(1/h) 0.0559 0.0390 39.77 0.0518 0.0352 68.04
t1/2(h) 12.9 20.20 156.65 14.84 22.95 154.62
AUC0-∞ (h*IU/dL) 935.02 922.54 98.67 2521.82 1988.78 78.86
CL/F(dL/h) 2.04 2.08 102.3 2.47 3.44 139.39
IVR([IU/dL]/[IU/kg]) 2.73 2.14 78.23 2.06 1.47 71.1

[Table 1]

Conclusions: In this phase I clinical study, FRSW107 shows no safety issues and is well tolerated in PTPs. The half- life of FRSW 107 is significantly extended compared with conventional rFVIII. The PK and pharmacodynamics of FRSW107 will be further determined in future phase III clinical trial.

To cite this abstract in AMA style:

Xue F, Chen Y, Wen Q, Sun J, Xu C, Zhang X, Sun H, Wang Y, Su H, Yang R. Extended Half-Life of the Double-Chain Recombinant Factor VIII-Fc Fusion Protein (FRSW107) in Previous Treated Hemophilia A Patients [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/extended-half-life-of-the-double-chain-recombinant-factor-viii-fc-fusion-protein-frsw107-in-previous-treated-hemophilia-a-patients/. Accessed October 2, 2023.

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