David Lillicrap, MD, FRCPC
Highlights From the ISTH 2021 Congress

Investigation of Early Outcomes Following Adeno-associated Viral Gene Therapy in a Canine Hemophilia Model

P. Batty1, B. Yates2, D. Hurlbut3, S. Siso-Llonch2, A. Menard3, H. Akeefe2, T. Christianson2, P. Colosi2, L. Harpell1, S. Liu2, A. Mo1, A. Pender1, G. Veres2, C. Vitelli2, A. Winterborn4, S. Bunting2, S. Fong2, D. Lillicrap1

1Department of Pathology and Molecular Medicine, Queen's University, Kingston, Canada

2BioMarin Pharmaceutical, Novato, United States

3Kingston Health Sciences, Kingston, Canada

4Animal Care Services, Queen's University, Kingston, Canada

Key Data Points

Data Points

A hemophilia A dog model was used to evaluate changes affecting the liver and factors affecting FVIII expression following AAV gene therapy. Five male dogs were treated with a single infusion of AAV5-HLP-cFVIII at doses of 6.8e13–2e14 vector genomes/kg. FVIII expression was seen for the 2 dogs treated with codon-optimized constructs (JA2013 and K2015), which was sustained at six months (co-cFVIII-SQ = 6.8% and co-cFVIII-V3 = 4.3%) with normalization of the whole blood clotting time (WBCT).

Data Point 2
As seen in this graph, the dog treated with co-cFVIII-V3 (K2015) developed two episodes of transaminitis, a mild post-biopsy elevation at day 84, and a second larger elevation at day 116, just before the second biopsy. Ultrasound imaging and liver biopsies used to investigate these episodes demonstrated no significant underlying liver histopathology.


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Supported by educational grants from Bayer, BioMarin, CSL Behring, Freeline Therapeutics Limited, Pfizer Inc., Spark Therapeutics, and uniQure, Inc.

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