OC 24.5 - A Phase 1 Study to Evaluate the Pharmacokinetics and Safety of a PEGylated-Recombinant Human Coagulation Factor VIII-Fc Fusion Protein in Patients With Severe Hemophilia A

Sunday, June 25, 2023

15:45 – 16:00 ET

Room: 520

Session Available As: On-Demand

Co-Author(s)

Feng Xue, MD

Chief physician
Institute of haematology and Blood Diseaes Hospital, Chinese Academy of Medical Sciences and Pkeing Union Medical College
Tianjin, Tianjin, China (People's Republic)

Co-Author(s)

YC

Yun Chen

Physician
Jinan central hospital, Shandong, P.R. China
Jinan, Shandong, China (People's Republic)
JS

Jing Sun

Chief Physician
Nanfang Hospital of Southern Medical University, Guangzhou, P.R. China
Tianjin, Tianjin, China (People's Republic)
SG

Shuxia Guo

Physician
Zhengzhou People's Hospital
zhengzhou, Henan, China (People's Republic)
QW

Qing Wen

Physician
Jinan central hospital, Shandong, P.R. China
Jinan, Shandong, China (People's Republic)
CX

Chongyuan Xu

Physician
Nanfang Hospital of Southern Medical University, Guangzhou, P.R. China
Guangzhou, Guangdong, China (People's Republic)
PL

Ping Liu

physician
Zhengzhou People's Hospital
Zhengzhou, Henan, China (People's Republic)

Presenting Author(s)

Renchi Yang, MD (he/him/his)

Professor
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Tianjin, Tianjin, China (People's Republic)

Background: Factor VIII (FVIII) replacement therapy of severe hemophilia A (HA) necessitates multiple doses of FVIII products weekly to maintain a > 1% FVIII trough activity due to their short half-life. FRSW117 is a PEGylated FVIII Fc fusion protein engineered to extend its half-life to maintain a sufficient FVIII level and improve treatment outcomes.

Aims: To evaluate the pharmacokinetics, safety/tolerability, and immunogenicity of FRSW117 in patients with severe HA.

Methods: In this first-in-human, open label, single dose, self-controlled study, 13 previously treated males aged 12 (inclusive) to 65 years with severe HA (FVIII < 1%) were enrolled to receive ADVATE® followed by FRSW117, both at 25 IU/kg, 4 days apart (N=6, Group S1); or both drugs at 50 IU/kg, 6 days apart (N=7, Group S2), followed by a 4-week follow-up after FRSW117 injection. All patients provided written informed consents. The protocol was approved by each site’s IEC/IRB.(ClinicalTrials.gov identifier: NCT04864743)

Results: The maximum concentration (Cmax) and area under the curve (AUC0-t) of FⅧ activity increased in a dose-dependent manner (Figure 1). The geometric mean elimination half-life of FRSW117 exceeded twice that of ADVATE® (30.928 hours vs. 13.668 hours in S1; 30.801 hours vs. 14.007 hours in S2) (Table 1). The mean FVIII level was > 5% for 101.527 hours in S1 and 138.145 hours in S2. Both groups maintained an FVIII activity of > 1% for longer than 168 hours (7 days), 176.769 hours for S1 and 206.253 hours for S2. No FⅧ inhibitors were detected and no hypersensitivity or anaphylaxis were reported. No serious adverse events or ≥ Grade 3 adverse events were reported. No spontaneous bleeding requiring intervention was reported within 9 days after FRSW117 treatment.

Conclusion(s): FRSW117’s pharmacokinetic characteristics supported a potential weekly treatment interval. It also displayed favorable safety/tolerability and immunogenicity profiles.

Learning Objectives:

Upon completion, participants will be able to know the mechanism of extended half- life of a PEGylated-Recombinant Human Coagulation Factor VIII-Fc Fusion Protein.
Upon completion, participants will be able to know the PK of a PEGylated-Recombinant Human Coagulation Factor VIII-Fc Fusion Protein.
Upon completion, participants will be able to improve their knowlege about the role of extended half-live factor VIII in hemophilia.