Report on 4 cases with decreased recovery due to neutralizing antibodies specific for PEGylated recombinant factor VIII

Hillarp, Andreas; Holme, Pål A.; Wåland, Erik P.; Le, Marie S.; Henriksson, Carola E.; Tjønnfjord, Geir E.; Måseide, Ragnhild J.

doi:10.1016/j.jtha.2023.07.019

Cited by 3 publications

(2 citation statements)

References 13 publications

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“…Recently, several papers indicated that antibodies binding to PEG could potentially affect the in vivo IR of PEGylated FVIII given to patients 42 , 43 , 44 and could even induce inhibitory activities resulting in the neutralization of PEGylated FVIII in vitro and in vivo. 32 Pezeshkpoor et al 32 presented data indicating that antibodies against the PEG moiety of a 40PEG-BDD FVIII drug (B-domain–deleted FVIII PEGylated with a 40-kDa PEG) abolished the efficacy of the drug.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity profile of rurioctocog alfa pegol in previously treated patients with severe congenital hemophilia A

Horling,

Reipert,

Allacher

et al. 2024

Blood Advances

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Rurioctocog alfa pegol is an extended half-life full-length recombinant factor VIII (FVIII) bound to 20 kDa polyethylene glycol (PEG) that has been shown to be well tolerated and efficacious in the treatment and prevention of bleeding events in previously treated patients with severe hemophilia A. Here, we present a comprehensive analysis of immunogenicity data collected during 6 clinical studies of rurioctocog alfa pegol including a total of 360 unique previously treated patients with severe hemophilia A. The analysis included treatment-emerging FVIII neutralizing antibodies (FVIII inhibitors), pre-existing and treatment-emerging antibodies binding to FVIII, PEG-FVIII, or PEG, and treatment-emerging antibodies binding to Chinese hamster ovary host cell proteins. Moreover, the potential association between the presence of these binding antibodies and adverse events (AEs) observed in patients was investigated and the potential impact of these antibodies on the incremental recovery of rurioctocog alfa pegol in patients was analyzed. Overall, the data indicate that rurioctocog alfa pegol is not associated with any unexpected immunogenicity characteristics. One of the 360 patients developed a transient FVIII inhibitor with a titer of 0.6 BU/mL, which was not associated with any serious AEs. Antibodies binding to FVIII, PEG-FVIII, or PEG were not detected at the time when the inhibitor was present. Moreover, 54 of the 360 patients either entered the clinical studies with pre-existing binding antibodies or developed these antibodies after exposure to rurioctocog alfa pegol. These antibodies were transient in most patients and did not show any causal relationship to either AEs or spontaneous bleeding episodes.

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Section: Discussionmentioning

confidence: 99%

Immunogenicity profile of rurioctocog alfa pegol in previously treated patients with severe congenital hemophilia A

Horling,

Reipert,

Allacher

et al. 2024

Blood Advances

View full text Add to dashboard Cite

show abstract

“…Conversely, the mRNA vaccine against SARS-CoV-2 contains polyethylene glycol (PEG) on the surface of the lipid nanoparticle (LNP), which is suspected as one of the causative agents of anaphylaxis [ 8 , 9 ]. PEG has been known as the cause of an unexpected immunogenic response named the accelerated blood clearance (ABC) phenomenon, resulting in the increased clearance and reduced efficacy of PEG-conjugated drugs such as PEGylated recombinant factor Ⅷ products and pegylated granulocyte colony-stimulating factor [ [10] , [11] , [12] ]. However, it is not well known whether the presence or absence of anti-PEG antibodies before vaccination affects the vaccine efficacy or whether they are induced after vaccination.…”

Section: Introductionmentioning

confidence: 99%

Humoral immune response against SARS-CoV-2 and polyethylene glycol elicited by anti-SARS-CoV-2 mRNA vaccine, and effect of pre-existing anti-polyethylene glycol antibody in patients with hematological and autoimmune diseases

Hori,

Shimizu,

Ando

et al. 2024

Heliyon

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Variability in combinations of APTT reagent and substrate plasma for a one‐stage clotting assay to measure factor VIII products

Suzuki,

Kanematsu

et al. 2024

Int J Lab Hematology

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IntroductionAn investigation of the suitability of reagents for measuring FVIII products in a one‐stage clotting assay (OSA) showed variations in their FVIII activity (FVIII:C). Most studies have focused on the activated partial thromboplastin time (APTT) reagent rather than FVIII‐deficient plasma (F8DP), even though the APTT‐based OSA is comprised of APTT reagents and factor‐deficient plasma.AimA single‐centre study was conducted to clarify variations in measurements of FVIII products in an OSA using a total of 12 reagent combinations, including four APTT reagents and three types of F8DP.MethodsFVIII:C in nine types of FVIII product‐spiked plasma was measured using an OSA with four different APTT reagents and three types of F8DP.ResultsF8DP‐dependent variations were found in addition to differences derived from APTT reagents. Variations in target recovery (TR) were observed for NovoEight®, Eloctate®, and Jivi®. Reduced TR for Jivi was found only for Pathromtin SL in combination with congenital F8DP (F8DP‐3). This lower TR was not observed with alternative manufacturing lots of F8DP‐3. The reduced TR for Jivi might be related to impaired contact activation due to lower factor XI activity in F8DP‐3.ConclusionIn addition to APTT reagents, variations in F8DPs used for OSAs can also affect FVIII:C results. F8DPs as well as the APTT reagent used for OSA should be chosen with caution, and laboratories should evaluate reagents for F8DPs as they currently do for APTT reagents, especially when lot changes occur.

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Report on 4 cases with decreased recovery due to neutralizing antibodies specific for PEGylated recombinant factor VIII

Cited by 3 publications

References 13 publications

Immunogenicity profile of rurioctocog alfa pegol in previously treated patients with severe congenital hemophilia A

Immunogenicity profile of rurioctocog alfa pegol in previously treated patients with severe congenital hemophilia A

Humoral immune response against SARS-CoV-2 and polyethylene glycol elicited by anti-SARS-CoV-2 mRNA vaccine, and effect of pre-existing anti-polyethylene glycol antibody in patients with hematological and autoimmune diseases

Variability in combinations of APTT reagent and substrate plasma for a one‐stage clotting assay to measure factor VIII products

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