OC 21.2 - Hemostatic results for up to 6 years following treatment with valoctocogene roxaparvovec, an AAV5-hFVIII-SQ gene therapy for severe hemophilia A

Sunday, July 10, 2022

3:00 PM – 3:15 PM

Location: ExCel Center, S11A

Presentation Format: In-Person

Presenting Author(s)

Michael A. Laffan, MD

Professor
Centre for Haematology, Imperial College London, London, UK
London, England, United Kingdom

Co-Author(s)

Savita Rangarajan, MD, FRCP, FRCPath

Associate Professor of Clinical Haematology
Faculty of Medicine, University of Southampton, Southampton, UK
Southampton, England, United Kingdom
WL

Will Lester

Consultant Haematologist
University Hospitals Birmingham NHS Foundation Trust
Birmingham, England, United Kingdom
ES

Emily Symington

Consultant Haematologist
Cambridge University Hospitals NHS Foundation Trust
Cambridge, England, United Kingdom
Bella Madan, MD FRCP FRCPath

Consultant Haematologist
Guy's & St. Thomas’ NHS Foundation Trust, London, UK
London, England, United Kingdom
Dan P. Hart, BSc, MBChB, MRCP, FRCPath

Senior Clinical Lecturer in Haematology & Honorary Consultant in Haematology
The Royal London Hospital Haemophilia Centre, Barts and The London School of Medicine and Dentistry
London, England, United Kingdom
ML

Mingjin Li

Associate Director, Biostatistics
BioMarin Pharmaceutical Inc.
Novato, California, United States
TR

Tara M. Robinson

Medical Director, Clinical Science
BioMarin Pharmaceutical Inc., Novato, CA, USA
Novato, California, United States
GP

Glenn F. Pierce, MD

Consultant
Independent
La Jolla, California, United States
WW

Wing Yen Wong

Head of Global Medical Affairs
BioMarin Pharmaceutical Inc.
Novato, California, United States

Background: Sustained clinical benefit was demonstrated up to 5 years following a single 6E13 vg/kg dose of valoctocogene roxaparvovec (AAV5-hFVIII-SQ), an investigational gene therapy for severe hemophilia A, in a Phase 1/2 trial (NCT02576795). All 7 participants showed sustained improvements in factor FVIII (FVIII) activity, annualized treated bleeding rate, and use of exogenous FVIII. Similar results were seen for up to 4 years in the 6 participants who received a 4E13 vg/kg dose. No participants chose to resume FVIII prophylaxis. Although these results indicate that valoctocogene roxaparvovec provides substantial hemostatic efficacy, longer follow-up is needed to monitor safety and determine how long the transgene will produce FVIII and protect against bleeding.

Aims: To report safety and efficacy of valoctocogene roxaparvovec up to 6 years after administration in a Phase 1/2 trial.

Methods: Adult male participants with severe hemophilia A who had previously been treated with FVIII received a single intravenous dose of valoctocogene roxaparvovec at 6E13 vg/kg (n=7) or 4E13 vg/kg (n=6).

Results: Updated, detailed safety and efficacy assessments from 6-year follow-up data from the 6E13 vg/kg cohort and 5-year follow-up data from the 4E13 vg/kg cohort will be shared at the ISTH 2022 Congress. Presented endpoints will include summary and individual participant FVIII activity, annualized treated bleeding and FVIII utilization rates, details of bleeding events, and adverse events.

Conclusion(s): The 6-year data from this Phase 1/2 study of valoctocogene roxaparvovec reported at ISTH 2022 will provide the most up-to-date, long-term follow-up data currently available for investigational use of AAV-mediated therapy for hemophilia A. Funded by BioMarin Pharmaceutical Inc.