Practical aspects of extended half-life products for the treatment of haemophilia

Abstract

Haemophilia A and haemophilia B are congenital X-linked bleeding disorders caused by deficiency of coagulation factor VIII (FVIII) and IX (FIX), respectively. The preferred treatment option for patients with haemophilia is replacement therapy. For patients with severe disease, prophylactic replacement of coagulation factor is the treatment of choice; this has been shown to reduce arthropathy significantly, reduce the frequency of bleeds and improve patients' quality of life. Prophylaxis with standard recombinant factor requires regular intravenous infusion at least two (FIX) to three (FVIII) times a week. Recombinant FVIII and FIX products with an extended half-life are in development, or have been recently licensed. With reported mean half-life extensions of 1.5-1.8 times that of standard products for FVIII and 3-5 times that of standard products for FIX, these products have the potential to address many of the unmet needs of patients currently treated with standard factor concentrates. For example, they may encourage patients to switch from on-demand treatment to prophylaxis and improve the quality of life of patients receiving prophylaxis. Indeed, extended half-life products have the potential to reduce the burden of frequent intravenous injections, reducing the need for central venous lines in children, promote adherence, improve outcomes, potentially allow for more active lifestyles and, depending on the dosing regimen, increase factor trough levels. Members of the Zürich Haemophilia Forum convened for their 19th meeting to discuss the practicalities of incorporating new treatments into the management of people with haemophilia. This review of extended half-life products considers their introduction in haemophilia treatment, including the appropriate dose and schedule of infusions, laboratory monitoring, patient selection, safety considerations, and the economic aspects of care.

Regional variation and cost implications of prescribed extended half‐life factor concentrates among U.S. Haemophilia Treatment Centres for patients with moderate and severe haemophilia

“…Protein modifications including Fc‐fusion and PEGylation have had a different impact on the circulation time of FVIII compared to that of FIX . The half‐life extension achieved by EHL FVIII CFCs is modest, averaging just 1.5 times that of SHL FVIII CFCs and thereby lengthening the infusion interval by only a day or two .…”

“…6,7 Protein modifications including Fc-fusion and PEGylation have had a different impact on the circulation time of FVIII compared to that of FIX. 8,9 The half-life extension achieved by EHL FVIII CFCs is modest, averaging just 1.5 times that of SHL FVIII CFCs and thereby lengthening the infusion interval by only a day or two. 10,11 EHL FIX CFCs offer a more robust improvement in circulating FIX activity with dosing frequency extended to weekly or every 2 weeks in some instances.…”

Pharmacokinetics, immunogenicity, safety, and preliminary efficacy of subcutaneous turoctocog alfa pegol in previously treated patients with severe hemophilia A (alleviate 1)

“…The availability of prophylactic FVIII replacement therapy has reduced the incidence of hemophilic arthropathy and overall morbidity and turned a life‐threatening disease into a chronic yet manageable condition . The life expectancy of people with hemophilia (PWH) is now approaching that of the general population, and new treatments are increasingly focused on reducing the burden of care . The introduction of extended half‐life (EHL) rFVIII therapies has increased bleed protection and FVIII trough levels, with potential for improved quality of life .…”

“…The life expectancy of people with hemophilia (PWH) is now approaching that of the general population, and new treatments are increasingly focused on reducing the burden of care . The introduction of extended half‐life (EHL) rFVIII therapies has increased bleed protection and FVIII trough levels, with potential for improved quality of life . Furthermore, EHL rFVIII therapies have improved convenience of prophylaxis because of the less‐frequent dosing regimens required, compared with standard half‐life products.…”

“…Furthermore, EHL rFVIII therapies have improved convenience of prophylaxis because of the less‐frequent dosing regimens required, compared with standard half‐life products. However, the relative increase in half‐life of currently available EHL FVIII products for hemophilia A treatment is only modest, compared with that of EHL factor IX (FIX) products used to treat hemophilia B . All EHL products are currently administered intravenously …”