321.

BLOOD COAGULATION AND FIBRINOLYTIC FACTORS: POSTER III | NOVEMBER 29, 2018

Development of a Pegylated Dimeric Recombinant Factor VIII-

Fc Fusion Protein for the Treatment for Hemophilia a Patients
*,1 *,1 *,1
Bin Liu, PhD, Xiaoshan Wang, Master, Xueqin Li, Master,
*,1 *,1 *,2 *,2
Haixia Yan, PhD, Shuya Wang, Master, Xi Zhu, Pengju Wang,
*,1 *,1 *,1
Jie Gao, Master, Yali Wang, PhD, Hongsheng Su, PhD
1
Beijing Furen Ruihui Biomedical Research Institute Co., Ltd, Beijing, China
2
Shanghai InnoStar Bio-Tech Co. Ltd (National Shanghai Center
for New Drug Safety Evaluation and Research), Shanghai, China

Blood (2018) 132 (Supplement 1) : 3783.

http://doi.org/10.1182/blood-2018-99-112030

Abstract

Hemophilia A is a hereditary bleeding disorder resulting from reduced factor FVIII activity. It occurred
in 1/5000 male. Currently, the treatment option is with the factor FVIII replacement therapy. A long-
acting recombinant monomeric FVIII-Fc fusion protein product (Eloctate®) has been approved in 2014
by the US FDA, it requires to infuse the drug for every 3 days or twice a week. There is a clinical need
to develop longer half-life product to extend the treatment option to once a week infuse for hemophilia A
patients. Recently, we have developed a dimeric recombinant factor VIII-Fc (drFVIII-Fc) fusion protein
therapeutic candidate, which is entering the clinical development in China. To generate a longer half-
life recombinant FVIII product, we have developed a PEGylation method to PEGylated this drFVIII-Fc
fusion protein to PEGdrFVIII-Fc. We have analyzed and characterized the fusion protein by various
analytic methods, as well as in vivo animal tests. It was shown that PEGdrFVIII-Fc fusion protein has
been modified with about five Y type of 40kd PEG; the remaining activity is around 700 IU/mg, and the in
vivo tests in cynomolgus monkey demonstrated that the fusion protein has a half-life of about 37 hours.
The data also showed that there was no detectable affinity binding activity of vWF to a PEGdrFVIII-Fc
fusion protein, as compared with the binding activity of 5.16X10-4M for the molecule of a drFVIII-Fc
fusion protein. In conclusion, we are able to generate a PEGylated form of a drFVIII-Fc molecule with the
relevant specific activity and has been shown the molecule with the prolonger half-life in the in vivo tests.
The further biochemical analysis demonstrated PEGdrFVIII-Fc fusion protein with no detectable vWF
binding activity, which might explain why its half-life is longer than vWF's ~15hours half-life in vivo. This
molecule is likely to be used as a once-weekly treatment option for hemophilia A patients. Currently, we
are in the development stage of an IND filing in China.

Disclosures

No relevant conflicts of interest to declare.

Author notes
* Asterisk with author names denotes non-ASH members.

This icon denotes a clinically relevant abstract

© 2018 by the American Society of Hematology