Development of Antidrug Inhibitory Antibodies against Polyethylene Glycol after Treatment with PEGylated Factor VIII Therapeutic

Pezeshkpoor, Behnaz; Sereda, Nadja; Berkemeier, Ann-Cristin; Schwarz, Robert; Müller, Jens; Albert, T.; Oldenburg, J.

doi:10.1055/s-0042-1758496

Cited by 2 publications

(7 citation statements)

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“… a Anti‐PEG antibody assays were performed using an in‐house method, and units are in BU 15 ; assays were positive for anti‐PEG IgG antibodies at 25 BU after exposure to N8‐GP.…”

Section: Resultsmentioning

confidence: 99%

“…The patient experienced a bleeding episode during the surgery. Anti‐PEG antibody assays were performed using an in‐house method 15 . Assays were positive for anti‐PEG IgG antibodies at 25 Bethesda units after exposure to N8‐GP.…”

Section: Resultsmentioning

confidence: 99%

“…13,14 In two cases, anti-PEG and anti-FVIII antibody assays were performed according to a method developed by the laboratory at the reporter's centre. 15…”

Section: Methodsmentioning

confidence: 99%

“…The anti‐PEG IgG and IgM were analysed using a direct enzyme‐linked immunosorbent assay 13,14 . In two cases, anti‐PEG and anti‐FVIII antibody assays were performed according to a method developed by the laboratory at the reporter's centre 15 …”

Section: Methodsmentioning

confidence: 99%

“…Abbreviations: BU, Bethesda units; FVIII, factor VIII; ED, exposure days; HA, haemophilia A; ITI, immune tolerance induction; N8-GP, turoctocog alfa pegol; PEG, polyethylene glycol. a Anti-PEG antibody assays were performed using an in-house method, and units are in BU15 ; assays were positive for anti-PEG IgG antibodies at 25 BU after exposure to N8-GP. b This patient also had pre-existing anti-PEG IgG (titre 1) and IgM (titre 4) antibodies.…”

mentioning

confidence: 99%

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Cases of less‐than‐expected FVIII activity in previously treated patients during post‐marketing surveillance of N8‐GP

Oldenburg,

Benson,

Chowdary

et al. 2023

Haemophilia

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IntroductionTuroctocog alfa pegol (N8‐GP) is a glycoPEGylated, extended half‐life (EHL), human recombinant factor VIII (FVIII) approved for the treatment and prevention of bleeding episodes in patients with haemophilia A. Since its launch in August 2019, > 800 patients have been treated worldwide.AimTo present data from identified post‐marketing cases of less‐than‐expected FVIII activity in previously treated patients (PTPs) without inhibitors after switching to N8‐GP.MethodsThe post‐marketing safety database was searched using keywords such as ‘coagulation FVIII level decreased’. Identified cases reported prior to 13 October 2021 were included in this report. Cases in which patients had FVIII inhibitors were excluded.ResultsHere we report 14 cases of less‐than‐expected FVIII activity. Details varied greatly amongst the cases. At presentation, FVIII activity ranged from 1% (15 min post‐dose) to 51% (2 days post‐dose). Seven patients experienced bleeding episodes after switching to N8‐GP with heterogeneity in bleeding presentations. Six out of seven patients who were tested for anti‐PEG IgG and/or IgM antibodies were positive. In all known cases, FVIII activity returned to the expected range when switched to an alternative FVIII replacement product.ConclusionIn conclusion, the 14 reported cases of less‐than‐expected FVIII activity, without presence of detectable FVIII inhibitors, presented with heterogenous characteristics, and wide variations in FVIII activity and anti‐PEG antibody titre. FVIII activity returned to the expected range after switching to alternative FVIII products. In line with WFH guidelines, monitoring of FVIII activity can ensure FVIII activity in the expected range. The safety surveillance of N8‐GP continues.

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“… a Anti‐PEG antibody assays were performed using an in‐house method, and units are in BU 15 ; assays were positive for anti‐PEG IgG antibodies at 25 BU after exposure to N8‐GP.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…13,14 In two cases, anti-PEG and anti-FVIII antibody assays were performed according to a method developed by the laboratory at the reporter's centre. 15…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Cases of less‐than‐expected FVIII activity in previously treated patients during post‐marketing surveillance of N8‐GP

Oldenburg,

Benson,

Chowdary

et al. 2023

Haemophilia

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Two‐center validation of assays for the detection of binding and neutralizing anti‐factor VIII antibodies

Müller,

Neimanis,

Kahle

et al. 2023

Haemophilia

Self Cite

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IntroductionPatients with hemophilia A treated with coagulation Factor VIII (FVIII) products are at risk for developing anti‐FVIII antibodies. The ABIRISK Consortium aimed to provide knowledge on the formation and detection of anti‐drug antibodies against biopharmaceutical products, including FVIII. Accordingly, standardized and validated assays for the detection of binding (total) and neutralizing antibodies are needed.AimTwo‐center validation of an ELISA for the detection of total FVIII‐binding IgG‐antibodies and Nijmegen‐Bethesda assays for the quantification of FVIII‐neutralizing antibodies according to consensus validation guidelines.MethodsValidation of assays at both sites was done according to published recommendations and included preanalytics, the determination of key assay parameters, including cut‐points, assay sensitivity, precision, and FVIII interference.ResultsThe validated assays reproducibly detected FVIII‐binding and ‐neutralizing antibodies with comparable performance in both laboratories. Floating screening cut‐points were established for both assays. Determined mass‐based sensitivity of both assays (all values ≤66 ng/mL) complied with the minimum sensitivity for the detection of anti‐drug antibodies as recommended by the FDA (<100 ng/mL). Intra‐ and inter‐assay coefficients of variation did not exceed 25%. Assay validation further revealed that pre‐analytical heat treatment led to potentially false‐positive ELISA results, while up to 0.15 IU/mL, residual FVIII showed no significant impact. Overall, good agreement of results was found for patient samples analyzed at both study sites.ConclusionComprehensive validation of different anti‐FVIII‐antibody assays in two laboratories gave novel insights into the impact of pre‐analytical sample treatment as well as the comparability of test results generated by the use of methodically different assays.

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Development of Antidrug Inhibitory Antibodies against Polyethylene Glycol after Treatment with PEGylated Factor VIII Therapeutic

Cited by 2 publications

References 0 publications

Cases of less‐than‐expected FVIII activity in previously treated patients during post‐marketing surveillance of N8‐GP

Cases of less‐than‐expected FVIII activity in previously treated patients during post‐marketing surveillance of N8‐GP

Two‐center validation of assays for the detection of binding and neutralizing anti‐factor VIII antibodies

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