Relationship Between Endogenous, Transgene FVIII Expression and Bleeding Events Following Valoctocogene Roxaparvovec Gene Transfer for Severe Hemophilia A: A Post-Hoc Analysis of the GENEr8-1 Phase 3 Trial
Highlights From the 63rd ASH Annual Meeting

Relationship Between Endogenous, Transgene FVIII Expression and Bleeding Events Following Valoctocogene Roxaparvovec Gene Transfer for Severe Hemophilia A: A Post-Hoc Analysis of the GENEr8-1 Phase 3 Trial

Steven W. Pipe, MD1, Margareth C Ozelo, MD, PhD2*, Gili Kenet, MD3, Mark T Reding, MD4, Jane Mason, MBBS Hons, FRACP, FRCPA5,6*, Andrew D Leavitt, MD7, Bella Madan, MD8*, Michael Laffan, DM, PhD9, Doris V. Quon10, Annette von Drygalski, MD, Pharm D11, Sheng-Chieh Chou, MD, PhD12*, Susan Shapiro, MD, PhD13,14,15*, Amy L Dunn, MD16*, Michael Wang, MD17, Nigel S Key18, Radoslaw Kaczmarek, PhD19,20*, Emily Symington, MD21*, Adebayo Lawal, MD, MSc, MBA22*, Reena Mahajan, MD22*, Konstantia-Maria Chavele, PhD22*, Divya B Reddy, MD22*, Hua Yu, PhD22*, Wing Yen Wong, MD22*, Tara M Robinson, MD, PhD22*, and Benjamin Kim, MD, MPhil22

1Department of Pediatrics and Pathology, University of Michigan, Ann Arbor, MI
2Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil
3The National Hemophilia Center, and Amalia Biron Research Institute of Thrombosis and Haemostasis, Sheba Medical Center, Tel Hashomer, Tel Aviv University, Tel Aviv, Israel
4Center for Bleeding and Clotting Disorders, University of Minnesota Medical Center, Minneapolis, MN
5University of Queensland, Brisbane, QLD, Australia
6Queensland Haemophilia Centre, Cancer Care Services, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
7University of California San Fransico, San Francisco, CA
8Guy's & St. Thomas' NHS Foundation Trust, London, United Kingdom
9Centre for Haematology, Department of Medicine, Imperial College London, London, United Kingdom
10Orthopaedic Hemophilia Treatment Center, Los Angeles, CA
11Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA
12Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
13Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
14Oxford University Hospitals National Health Service Foundation Trust, Oxford, United Kingdom
15National Institute for Health Research, Oxford Biomedical Research Centre, Oxford, United Kingdom
16Hemophilia Treatment Center, Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, OH
17Hemophilia and Thrombosis Center, University of Colorado Anschutz Medical Campus, Aurora, CO
18UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC
19Department of Pediatrics, Indiana University School of Medicine, IUPUI-Wells Center for Pediatric Research, Indianapolis, IN
20Laboratory of Glycobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland
21Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
22BioMarin Pharmaceutical Inc., Novato, CA

Key Data Points

Phase 3 GENEr8-1 study design

Results from the phase 3 GENEr8-1 study were analyzed for the relationship between transgene-derived FVIII activity and bleeds. Of the total number of participants in the study (N = 134), this analysis included a subset of patients who experienced ≥ 1 treated bleed in the post-transition period, which started 1 month after the end of the post-prophylaxis period that followed infusion of transgene.

ABR in participants with treated bleeds post-transition (n = 22)

Of 134 total participants in the GENEr8-1 study, 22 (16%) experienced at least 1 treated bleed in the post-transition period. ABR is shown for these participants for the pre-infusion baseline and the post-infusion, post-prophylaxis study period. Relative to baseline, 15 participants had a decrease in ABR, 2 had an increase in ABR < 1 (black arrows) and 5 had an increase in ABR > 1 (orange arrows).


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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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