What question did this study set out to answer?

The review aims to summarize the advancements in extended half-life (EHL) factor concentrates for haemophilia A and B treatment.

March 12, 2026Open Access

Extended Half-Life Factor Concentrates in Haemophilia Treatment

KHKatharina HolsteinUniversity Hospital Schleswig-Holstein TBTido BajoratClinical Research Center Kiel RBRafael BeckUniversity Hospital Schleswig-Holstein

Key Points

The review aims to summarize the advancements in extended half-life (EHL) factor concentrates for haemophilia A and B treatment.
Reviewed existing literature on EHL and its mechanisms of action including Fc-fusion and PEGylation.
Analysed clinical trial data related to EHL factor concentrates and their real-world applications.
Evaluated safety aspects of EHL, especially in young children with respect to PEG-related concerns.
EHL factor concentrates allow for less frequent infusions and significantly reduce annual bleed rates (ABR).
Patients using EHL reported better joint health and higher quality of life than those on standard half-life concentrates.
Inhibitor rates in previously treated patients are low, with some evidence suggesting similar or lower rates compared to standard half-life therapies.

Abstract

Background: For prevention of musculoskeletal bleeds in patients with severe and moderate haemophilia A (HA) or B (HB), prophylaxis is recommended. Clotting factor concentrates with standard half-life (SHL) necessitate frequent infusions associated with high treatment burden, leading to the development of extended half-life factor concentrates (EHL) and Non-Factor-Therapies (NFT). Summary: This review aims to summarise knowledge on EHL for haemophilia A and B. Those employ Fc-fusion, albumin fusion or PEGylation to extend half-life and reduce clearance. Half-life extension for factor VIII (FVIII) has been limited due to binding to and elimination with endogenous von Willebrand factor (VWF). With linking the FVIII molecule to a D’D3 domain of the VWF, binding to endogenous VWF is inhibited, enabling the development of a FVIII concentrate with ultra-long half-life. EHL allow less frequent prophylaxis, and clinical trials and real-world data show reduced ABR, better joint outcomes, improved adherence and better patient-reported health-related quality of life. Inhibitor rates in previously treated patients (PTPs) are very low and seem to be similar or lower compared to SHL recombinant FVIII (rFVIII) in previously untreated patients (PUPs), but robust head-to-head comparative data are limited. Close monitoring remains essential. For PEG-containing products, extensive non-clinical and clinical experience has not identified clear PEG-related organ toxicity in humans, but theoretical concerns about life-long exposure, rare anti-PEG antibody-mediated loss of efficacy, and potential tissue accumulation mean that careful pharmacovigilance and monitoring of recovery and clinical response are still recommended, especially in young children. Key messages: EHL enable efficacious and safe prophylaxis as well as bleed treatment with the possibility of individualisation. With improved ABRs, joint health and low treatment burden, they prove clinical benefit compared to SHL and coexist with NFT.

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