Efficacy and Safety of Valoctocogene Roxaparvovec Adeno-associated Virus Gene Transfer for Severe Hemophilia A: Results From the Phase 3 GENEr8-1 Trial

Highlights From the ISTH 2021 Congress

Efficacy and Safety of Valoctocogene Roxaparvovec Adeno-associated Virus Gene Transfer for Severe Hemophilia A: Results From the Phase 3 GENEr8-1 Trial

M.C Ozelo¹, J. Mahlangu², KJ. Pasi³, A. Giermasz⁴, A.D Leavitt⁵, M. Laffan⁶, E. Symington⁷, D.V Quon⁸, J.-D. Wang⁹, K. Peerlinck¹¹, S. Pipe¹¹, B. Madan¹², N.S Key¹³, G.F Pierce¹⁴, B. O’Mahony^15,16, R. Kaczmarek^17,18, A. Lawal¹⁹, M. Huang¹⁹, W.Y. Wong¹⁹, B. Kim¹⁹, GENEr8-1 Trial Group

¹Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil

²Hemophilia Comprehensive Care Center, Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand and NHLS, Johannesburg, South Africa

³Barts and the London School of Medicine and Dentistry, London, United Kingdom

⁴Hemophilia Treatment Center, University of California Davis, Sacramento, United States

⁵University of California, San Francisco, United States

⁶Centre for Haematology, Imperial College London, London, United Kingdom

⁷Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom

⁸Orthopaedic Hemophilia Treatment Center, Los Angeles, United States

⁹Center for Rare Disease and Hemophilia, Taichung Veterans General Hospital, Taichung, Taiwan, Province of China

¹⁰Department of Vascular Medicine and Haemostasis and Haemophilia Centre, University Hospitals Leuven, Leuven, Belgium

¹¹Departments of Pediatrics and Pathology, University of Michigan, Ann Arbor, United States

¹²Guy's & St. Thomas’ NHS Foundation Trust, London, United Kingdom

¹³UNC Blood Research Center, University of North Carolina, Chapel Hill, United States

¹⁴Independent Consultant, La Jolla, United States

¹⁵Irish Haemophilia Society, Dublin, Ireland

¹⁶Trinity College, Dublin, Ireland

¹⁷Department of Pediatrics, Indiana University School of Medicine, IUPUI-Wells Center for Pediatric Research, Indianapolis, United States

¹⁸Laboratory of Glycobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland

¹⁹BioMarin Pharmaceutical Inc., Novato, United States

Key Data Points

FVIII Activity Over 52 Weeks in mITT Population

FVIII activity using the chromogenic assay for patients (N = 132) in the phase 3 GENEr8-1 Trial treated with a single infusion of valoctocogene roxaparvovec (6 x 10¹³ vg/kg). At weeks 49–52, mean (95% CI) change from baseline in FVIII activity was 41.9 (34.1–49.7) IU/dL (P < 0.001), and median (Q1, Q3) change from baseline was 22.9 (10.9, 61.3) IU/dL.

Annualized bleed rate (ABR, left panel) and number of FVIII infusions/year (right panel) for the rollover population (n = 112) in the GENEr8-1 trial. For ABR, the mean (95% CI) change was a decrease of 4.1 (-5.3 to -2.8) treated bleeding events/year, a reduction of 83.8% from baseline. The mean change in infusions/year was 134 (-144 to -124), a decrease of 98.6% from baseline. Post-infusion was defined as starting after week 4.

Annualized bleed rate (ABR, left panel) and number of FVIII infusions/year (right panel) for the rollover population (n = 112) in the GENEr8-1 trial. For ABR, the mean (95% CI) change was a decrease of 4.1 (-5.3 to -2.8) treated bleeding events/year, a reduction of 83.8% from baseline. The mean change in infusions/year was 134 (-144 to -124), a decrease of 98.6% from baseline. Post-infusion was defined as starting after week 4.