Recombinant factor VIII Fc for the treatment of haemophilia A

Abstract

Prophylaxis with factor VIII (FVIII) is the current therapeutic approach for people with haemophilia A. However, standard half-life (SHL) FVIII products must be injected frequently, imposing a substantial burden on the individual and making it difficult to tailor therapy according to patient need and lifestyle, which could impact adherence. Recombinant FVIII Fc fusion protein (rFVIIIFc; Elocta^® , Sobi; Eloctate^® , Sanofi) is a recombinant fusion protein that undergoes slower clearance from the body than SHL FVIII products. This pharmacokinetic property of rFVIIIFc allows prophylactic administration every 3-5 days, or once weekly in selected patients, with doses adjusted to patient needs and clinical outcomes. Higher FVIII levels can be achieved maintaining dosing frequency similar to that usually applied with SHL FVIII. This review provides a summary of recent data from the A-LONG, Kids A-LONG, ASPIRE and PUPs A-LONG studies and recently published real-world experience relevant to rFVIIIFc use in individualised regimens. The review also introduces ongoing studies of rFVIIIFc, including its use for induction of immune tolerance, and discusses some aspects to consider when switching patients to rFVIIIFc and managing ongoing treatment. In summary, rFVIIIFc is suitable for individualised prophylaxis regimens that can be tailored according to patient clinical needs and lifestyle.

Keywords: factor VIII; factor VIII-Fc fusion protein; haemophilia A; half-life; immune tolerance; prophylaxis; rFVIIIFc; recombinant fusion proteins; surgical haemostasis.

FIGURE 1

Overview of key interventional clinical trials and prospective, non‐interventional, real‐world studies. Abbreviations: ABR, annualised bleeding rate; ITI, immune tolerance induction; N, study sample size (according to clinicaltrials.gov); FVIII, factor VIII; rFIXFc, recombinant factor IX Fc; rFVIIIFc, recombinant factor VIII Fc

FIGURE 2

Structural components of rFVIIIFc. ¹² , ¹³ Adapted from McCue J, et al. Biologicals. 2015;43:213‐219. https://doi.org/10.1016/j.biologicals.2015.05.012. Copyright © 2015 Biogen. Published by Elsevier Ltd.; published under the terms of the Creative Commons CC‐BY 4.0 licence available at: https://creativecommons.org/licenses/by/4.0/. Abbreviations: FVIII, factor VIII; rFVIIIFc, recombinant factor VIII Fc

FIGURE 3

ABR in children in Kids A‐LONG ²³ divided according to whether they had at least one target joint or no target joints at baseline. Abbreviations: ABR, annualised bleeding rate; IQR, interquartile range

FIGURE 4

Proportion of bleeding episodes resolved with use of either one or two injections of rFVIIIFc among patients in A‐LONG ¹⁶ and children in Kids A­LONG. ²³ Abbreviation: rFVIIIFc, recombinant factor VIII Fc

FIGURE 5

Overall change in physical activity among patients receiving prophylaxis in (A) A‐LONG and (B) Kids A‐LONG ²⁷

FIGURE 6

Mean changes in Haem‐A‐QoL scores (A and B) from baseline in A‐LONG to Mo 24 of ASPIRE. ²⁹ (A) Mean (standard error) change in Haem‐A‐QoL score in the individualised prophylaxis arm in ASPIRE; (B) Mean (standard error) changes in the physical health, sports and leisure, and feeling domains in the individualised prophylaxis arm in ASPIRE. (A/B): *P ≤ .01 compared with A‐LONG baseline score. NB. Data presented in graphs are mean (standard error) while data in the supporting tables for (A) and (B) are mean (standard deviation). Abbreviations: Haem‐A‐QoL, Haemophilia Quality of Life Questionnaire for Adults; n, number of observations at ASPIRE Mo 24

FIGURE 7

Triad of clinical factors that influence individualised prophylaxis with rFVIIIFc aiming for zero bleeding events in patients with severe haemophilia A. Abbreviation: rFVIIIFc, recombinant factor VIII Fc