Utilising Apheresis to Remove Neutralizing AAV Antibodies in Patients Previous Excluded From Gene Therapy
Highlights from the ASGCT 23rd Annual Meeting

Utilising Apheresis to Remove Neutralizing AAV Antibodies in Patients Previous Excluded From Gene Therapy

Jonathan H. Foley1, Erald Shehu1, Allison Dane1, Rose Sheridan1, Rebecca Alade1, Thorold Guy1, Jenny McIntosh2, Hattie Ollerton1, Sophie Williams1, Romuald Corbau1, Helen Jones2, Nathan Davies2, Andrew Davenport2, David Briggs3, Amit Nathwani2

1Freeline, Stevenage, United Kingdom

2University College London, London, United Kingdom

3NHS Blood and Transplant, Birmingham, United Kingdom

Key Data Points

Up to 70% of patients with hemophilia may express antibodies that prevent treatment with AAV vectors for gene therapy. This study shows that double filtration plasmapheresis (DFPP) can be used to reduce AAVS3 neutralizing antibody (NAb) titers to align with trial eligibility criteria.

Results from patients with or without consecutive DFPP cycles using bright luciferase transduction inhibition assay (BL-TIA). Consecutive cycles were more effective than non-consecutive cycles in reducing Nab titres. Regression analysis predicted that 5 cycles would reduce the starting AAVS3 NAb titre by 94%, which would enable treatment of 60% of patients.

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