Emerging benefits of Fc fusion technology in the context of recombinant factor VIII replacement therapy

• Type of Material: Article
• Authors: Shannon Meeks, Emory University; Sébastien Lacroix-Desmazes, Sorbonne Universite
• Language: English
• Date: 2020-09-03
• Publisher: Wiley
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors. Haemophilia published by John Wiley & Sons Ltd
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1111/hae.14123
• Title of Journal or Parent Work: Haemophilia
• Volume: 26
• Issue: 6
• Start Page: 958
• End Page: 965
• Grant/Funding Information: None declared
• Keywords: inflammation; haemophilia A; Risk-factors; FVIII-FC; Previously untreated patients; Hematology; prophylaxis; Science & Technology; immunomodulation; Immune tolerance induction; FVIII; Half-life; Intravenous immunoglobulin; bone resorption (MeSH terms); Regulatory T-cells; Life Sciences & Biomedicine; Protein RFVIIIFC; Inhibitor development; immune tolerance; Severe hemophilia
• Research Categories: Health Sciences, Rehabilitation and Therapy; Health Sciences, Oncology; Engineering, Biomedical; Health Sciences, Medicine and Surgery

Abstract

Although the primary reason for recombinant factor VIII Fc fusion protein (rFVIIIFc) development was to reduce treatment burden associated with routine prophylaxis, new evidence suggests additional benefits of Fc fusion technology in the treatment of people with haemophilia A. Preclinical research has been utilized to characterize the potential immunomodulatory properties of rFVIIIFc, including an ability to reduce inflammation and induce tolerance to factor VIII. This has since been expanded into clinical research in immune tolerance induction (ITI) with rFVIIIFc, results of which suggest the potential for rapid tolerization in first-time ITI patients and therapeutic benefit in patients undergoing rescue ITI. The potential for improved joint health through the anti-inflammatory properties of rFVIIIFc has also been suggested. In addition, a new avenue of research into the role of rFVIIIFc in promoting bone health in patients with haemophilia A, potentially through reduced osteoclast formation, has yielded encouraging results that support further study. This review summarizes the existing preclinical and clinical studies of immunomodulation and tolerization with rFVIIIFc, as well as studies in joint and bone health, to elucidate the potential benefits of rFVIIIFc in haemophilia A beyond the extension of factor VIII half-life.