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.

Cost‐effectiveness of recombinant factor VIII Fc versus emicizumab for prophylaxis in adults and adolescents with haemophilia A without inhibitors in the UK

“…With regard to FVIII replacement therapy, the flexibility of treatment allows patients with haemophilia A to tailor treatment to their lifestyle and clinical profile. rFVIIIFc can be administered 3–4 times per week to maintain higher FVIII levels for patients who are physically active or those with joint damage, or it can be administered less frequently (every 3–5 days) to maintain FVIII levels similar to those of the more frequently dosed standard half‐life rFVIII 7 . A minimum target plasma trough level of 3%–5% FVIII activity is recommended to prevent breakthrough bleeding in patients with haemophilia A, and the ability to measure this is crucial in order to individualise prophylaxis regimens 26 …”

“…Primary prophylaxis with factor VIII (FVIII) replacement therapy is the recognised standard of care for patients with severe haemophilia A, 4 and UK guidelines recommend that this is initiated early in life, ideally before the second joint bleed, to preserve musculoskeletal function 5 . Extended half‐life (EHL) recombinant FVIII (rFVIII) replacement products are the favoured treatment option in the UK, and they can offer flexible dosing and the potential for individualised treatment to meet the needs of each patient 6,7 …”

“…5 Extended half-life (EHL) recombinant FVIII (rFVIII) replacement products are the favoured treatment option in the UK, and they can offer flexible dosing and the potential for individualised treatment to meet the needs of each patient. 6,7 One such EHL product, efmoroctocog alfa (a recombinant FVIII Fc fusion protein referred to herein as rFVIIIFc), has been shown to be well-tolerated and demonstrated low annualised bleeding rates (ABRs) among patients with severe haemophilia A receiving individualised prophylaxis in the open-label, multicentre trials, A-LONG and Kids A-LONG, and the long-term extension study, ASPIRE. [8][9][10] With the availability of the non-factor therapy, emicizumab, a recombinant humanised, bispecific, monoclonal antibody that mimics the function of activated FVIII, new options for patients with haemophilia A are now available.…”

Expert opinion on current and future prophylaxis therapies aimed at improving protection for people with hemophilia A

“…The final 11 multiple-choice questions were: ( 1 ) What laboratory assays are available in your practice? ( 2 ) How do challenges in laboratory monitoring of different therapies using different assays impact your therapy decision pathway in hemophilia A? ( 3 ) Reflecting your clinical practice, which parameters have you observed when introducing/switching a person with hemophilia to an EHL product, e.g.…”

The More Recent History of Hemophilia Treatment

“…[21][22][23] While albumin and Fc fusion prolong coagulation factor plasma half-life through avoidance of clearance by endolysosomal degradation, PEG, which is attached sitespecifically or randomly to coagulation factors, acts by reducing clotting factor susceptibility to proteolysis and renal elimination. [24][25][26] A number of extended half-life (EHL) recombinant FVIII and FIX coagulation factors have been licensed and marketed over the last 8 years (►Table 1). The strategies to improve pharmacokinetic parameters resulted in significant extensions of the half-life of FIX concentrates, usually three to five times longer than the standard half-life (SHL) of standard FIX products.…”