Updates from the GENEr8-1 Trial
Highlights From the 31th Congress of ISTH

Updates from the GENEr8-1 Trial

Presented by: Johnny Mahlangu, BSc, MBBCh, MMed, FCPath, Faculty of the Health Sciences-University of the Witwatersrand and National Health Laboratory Service, Johannesburg, South Africa

Bleeding, FVIII activity, and safety 3 years after gene transfer with valoctocogene roxaparvovec: Results from GENEr8-1

Johnny Mahlangu, BSc, MBBCh, MMed, FCPath

Faculty of the Health Sciences-University of the Witwatersrand and National Health Laboratory Service

Johannesburg, South Africa

Bleeding, FVIII activity, and safety 3 years after gene transfer with valoctocogene roxaparvovec: Results from GENEr8-1

Co-Authors:

Annette Von Drygalski, MD – University of California San Diego

Susan Shapiro, MD, PhD (she/her/hers) – Oxford University Hospitals National Health Service Foundation Trust, Oxford, UK

Sheng-Chieh Chou, MD. (he/him/his) – Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital

Margareth C. Ozelo, MD, PhD (she/her/hers) – Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil

Gili Kenet, MD – The National Hemophilia Center, and Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Tel Aviv University, Tel Aviv, Israel

Flora Peyvandi, MD, PhD (she/her/hers) – IRCCS Ca' Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy; Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milano, Italy

Bella Madan, MD FRCP FRCPath – Guy's & St. Thomas’ NHS Foundation Trust, London, UK

Michael A. Laffan, MD – Centre for Haematology, Imperial College London, London, UK

Amy L. Dunn – Oncology and Bone Marrow Transplant, Nationwide Children's Hospital and The Ohio State University College of Medicine, OH, USA

Jane Mason – Queensland Haemophilia Centre, Cancer Care Services, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia

Doris V. Quon, MD, PhD (she/her/hers) – Luskin Orthopaedic Institute for Children

Andrew D. Leavitt – Adult Hemophilia Treatment Center, University of California San Francisco, San Francisco, CA, USA

Johannes Oldenburg, MD (he/him/his) – University Clinic Bonn AöR, Institute of Experimental Haematology and Transfusion Medicine, Bonn, Germany

Hervé Chambost – AP-HM, Department of Pediatric Haematology Oncology, Children Hospital La Timone & Aix Marseille University, INSERM, INRA, C2VN, Marseille, France

Mark T. Reding – Center for Bleeding and Clotting Disorders, University of Minnesota, Minneapolis, MN, USA

Kala Jayaram – BioMarin Pharmaceutical Inc., Novato, CA, USA

Hua Yu – BioMarin Pharmaceutical Inc., Novato, CA, USA

Tara M. Robinson – BioMarin Pharmaceutical Inc., Novato, CA, USA

Steven W. Pipe, MD – University of Michigan, Ann Arbor, MI, USA



Gene Therapy in Hemophilia A: the Impact of Valoctocogene Roxaparvovec on Patient Outcomes – Initial Results from Patient Reported Outcomes, Burdens and Experiences (PROBE) from the GENEr8-1 Trial 

Presenting Author: Mark W. Skinner, JD – Institute for Policy Advancement Ltd.

Co-Authors:

Er Chen – BioMarin Pharmaceutical Inc.

Quazi Ibrahim – Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON

Alexandra Kucher – Patient Outcomes Research Group Ltd

Federico Germini, MD, MSc, PhD – Department of Medicine, McMaster University, Hamilton, ON

Milad Karimi – BioMarin Pharmaceutical Inc.

Elizabeth Clearfield – Institute for Policy Advancement Ltd.

Brian O'Mahony – Irish Haemophilia Society

Mohit Jain – BioMarin Pharmaceutical Inc.

Key Data Points

Reduction in Treated Bleeds Maintained Over 3 Years

Missing data were not imputed. aYear 3 data were based on N = 110 due to participants who discontinued from the study. ABR, annualized bleeding rate; SD, standard deviation; Q, quartile.

Graphic shows the analysis of treated bleeding events in the phase 3 GENEr8-1 study, which were analyzed in the rollover population to enable comparison with prior prophylaxis. On the left is ABR for treated bleeds before (baseline) and after treatment with valoctocogene roxaparovovec. There was an 82.9% reduction from baseline FVIII prophylaxis over all follow up to the most recent data cut date. The chart on the right shows that the proportion of participants with zero treated bleeds increased after treatment with valoctocogene roxaparovovec compared with baseline.

Gene Therapy in Hemophilia A: the Impact of Valoctocogene Roxaparvovec on Patient Outcomes – Initial Results from Patient Reported Outcomes, Burdens and Experiences (PROBE) from the GENEr8-1 Trial 

Presenting Author: Mark W. Skinner, JD – Institute for Policy Advancement Ltd.

Co-Authors:

Er Chen – BioMarin Pharmaceutical Inc.

Quazi Ibrahim – Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON

Alexandra Kucher – Patient Outcomes Research Group Ltd

Federico Germini, MD, MSc, PhD – Department of Medicine, McMaster University, Hamilton, ON

Milad Karimi – BioMarin Pharmaceutical Inc.

Elizabeth Clearfield – Institute for Policy Advancement Ltd.

Brian O'Mahony – Irish Haemophilia Society

Mohit Jain – BioMarin Pharmaceutical Inc.

 

PROBE Total Scores Improved at Weeks 52 and 104

***P <0.001 compared to baseline using a linear mixed model. Data are mean ± SD or change from baseline (95% CI). CI, confidence interval; PROBE, Patient Reported Outcomes, Burdens and Experiences; SD, standard deviation.  

In the GENEr8-1 trial for hemophilia A, HRQoL was assessed with the PROBE questionnaire. PROBE scores were available for 124/134 (93%) at baseline, 129/132 (98%) at week 52, and 129/130 (99%) at week 104. The chart on the left shows the aggregate mean for these time points. As shown in the left panel, average changes in score of 0.05 [95% CI: (0.03, 0.07), p < 0.001] and 0.05 (0.02, 0.07), p < 0.001) were observed at weeks 52 and 104, respectively.

RELATED CONTENT

Interactive Webinars
Image

Please enable the javascript to submit this form

Supported through educational grants from BioMarin, CSL Behring, Pfizer Inc., and Spark Therapeutics

Essential SSL