Hamostaseologie 2023; 43(S 01): S96
DOI: 10.1055/s-0042-1760620
Abstracts
Late breaking abstract

Efficacy and safety of valoctocogene roxaparvovec gene transfer for severe hemophilia A: results from the GENEr8-1 three-year analysis

J Mahlangu
1   Hemophilia Comprehensive Care Center, Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand and NHLS, Johannesburg, South Africa
,
A Drygalski von
2   Department of Medicine, University of California San Diego, CA, USA
,
S Shapiro
3   Oxford University Hospitals National Health Service Foundation Trust, Oxford, UK
4   Radcliffe Department of Medicine, University of Oxford, Oxford, UK
5   Oxford National Institute for Health Research Biomedical Research Centre, Oxford, UK
,
C Sheng-Chieh
6   Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
,
M Ozelo
7   Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil
,
G Kenet
8   The National Hemophilia Center, and Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Tel Aviv University, Tel Aviv, Israel
,
F Peyvandi
9   Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy
10   Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy
11   Guy's & St. Thomas’ NHS Foundation Trust, London, UK
,
B Madan
14   Queensland Haemophilia Centre, Cancer Care Services, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
,
M Laffan
12   Centre for Haematology, Imperial College London, London, UK
,
A Dunn
13   Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, OH, USA
,
J Mason
14   Queensland Haemophilia Centre, Cancer Care Services, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
15   University of Queensland, Brisbane, QLD, Australia
,
D Quon
16   Orthopaedic Hemophilia Treatment Center, Los Angeles, CA, USA
,
A Leavitt
17   University of California San Francisco, San Francisco, CA, USA
,
J Oldenburg
18   Institute of Experimental Haematology and Transfusion Medicine and Center for Rare Diseases, University Hospital Bonn, Bonn, Germany
,
H Chambost
19   AP-HM, Department of Pediatric Hematology Oncology, Children Hospital La Timone & Aix Marseille University, INSERM, INRA, C2VN, Marseille, France
,
M Reding
20   Center for Bleeding and Clotting Disorders, University of Minnesota, Minneapolis, MN, USA
,
K Jayaram
21   BioMarin Pharmaceutical Inc., Novato, CA, USA
,
H Yu
21   BioMarin Pharmaceutical Inc., Novato, CA, USA
,
T Robinson
21   BioMarin Pharmaceutical Inc., Novato, CA, USA
,
S Pipe
22   Departments of Pediatrics and Pathology, University of Michigan, Ann Arbor, MI, USA
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Introduction In August 2022, Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) received conditional marketing authorization from the European Medicines Agency for the treatment of severe hemophilia A in adult patients without a history of factor VIII inhibitors and without detectable antibodies to adeno-associated virus serotype 5 (AAV5). Stable and durable annualized bleed control superior to prior prophylaxis was previously demonstrated through 2 years post gene transfer. For the first time, we will report the latest findings from the Year 3 analysis of the ongoing GENEr8-1 study (NCT03370913).

Method GENEr8-1 is an open-label, multicenter phase 3 trial evaluating the efficacy and safety of 6x1013 vg/kg valoctocogene roxaparvovec in 134 adult men with severe hemophilia A (FVIII ≤1 IU/dL) without inhibitors or anti-AAV5 antibodies (ITT population). Of those, 132 were HIV negative (mITT population), and 112 enrolled from a prospective noninterventional study (rollover population), providing baseline data for annualized bleeding rate (ABR) and FVIII use. The primary efficacy endpoint was change from baseline in ABR for treated bleeds from 5 weeks post-infusion or 3 days after the end of FVIII prophylaxis, whichever was later, to the last visit by data cut-off. Change from baseline in annualized FVIII infusion rate (AFR) and FVIII activity will also be reported for week 156.

Results Updated efficacy and safety assessments from 3-year follow-up data will be shared at the GTH 2023 Congress. Presented endpoints will include FVIII activity, annualized treated bleed and FVIII utilization rates, patients who resumed FVIII prophylaxis, and adverse events.

Conclusions The 3-year data from the phase 3 GENEr8-1 study will provide the first opportunity for the hemophilia community to assess the long-term durability of valoctocogene roxaparvovec in a large cohort. These data will be of key interest to clinicians in Europe who may be considering whether to initiate gene therapy with valoctocogene roxaparvovec with their patients with severe hemophilia A.

Funding

Funded by BioMarin Pharmaceutical Inc.

Disclosures

Johnny Mahlangu, MBBCh, MMed

Johnny Mahlangu has received research grants from BioMarin, CSL, Novo Nordisk, Sobi, F. Hoffmann-La Roche Ltd, and Uniqure; and is a member of advisory committees for CSL Behring, Catalyst Biosciences, Novo Nordisk, F. Hoffmann-La Roche, and Spark Therapeutics.



Publikationsverlauf

Artikel online veröffentlicht:
20. Februar 2023

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