Health-related quality of life following valoctocogene roxaparvovec gene therapy for severe hemophilia A in the phase 3 trial GENEr8-1

Brian O'Mahony; Amy L Dunn; Andrew D Leavitt; Flora Peyvandi; Margareth C Ozelo; Johnny Mahlangu; Kathelijne Peerlinck; Jiaan-Der Wang; Gillian C Lowe; Chee Wee Tan; Adam Giermasz; Huyen Tran; Teh-Liane Khoo; Erin Cockrell; Dominic Pepperell; Hervé Chambost; Maria Fernanda López Fernández; Rashid Kazmi; Elaine Majerus; Mark W Skinner; Robert Klamroth; Jennifer Quinn; Hua Yu; Wing Yen Wong; Tara M Robinson; Steven W Pipe

doi:10.1016/j.jtha.2023.08.032

Health-related quality of life following valoctocogene roxaparvovec gene therapy for severe hemophilia A in the phase 3 trial GENEr8-1

J Thromb Haemost. 2023 Dec;21(12):3450-3462. doi: 10.1016/j.jtha.2023.08.032. Epub 2023 Sep 6.

Authors

Brian O'Mahony¹, Amy L Dunn², Andrew D Leavitt³, Flora Peyvandi⁴, Margareth C Ozelo⁵, Johnny Mahlangu⁶, Kathelijne Peerlinck⁷, Jiaan-Der Wang⁸, Gillian C Lowe⁹, Chee Wee Tan¹⁰, Adam Giermasz¹¹, Huyen Tran¹², Teh-Liane Khoo¹³, Erin Cockrell¹⁴, Dominic Pepperell¹⁵, Hervé Chambost¹⁶, Maria Fernanda López Fernández¹⁷, Rashid Kazmi¹⁸, Elaine Majerus¹⁹, Mark W Skinner²⁰, Robert Klamroth²¹, Jennifer Quinn²², Hua Yu²³, Wing Yen Wong²³, Tara M Robinson²³, Steven W Pipe²⁴

Affiliations

¹ Irish Haemophilia Society, Dublin, Ireland; Trinity College, Dublin, Ireland. Electronic address: brian@haemophilia.ie.
² The Division of Hematology, Oncology, and BMT at Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, Ohio, USA.
³ University of California San Francisco, San Francisco, California, USA.
⁴ Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy; Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy.
⁵ Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
⁶ Hemophilia Comprehensive Care Center, Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand and NHLS, Johannesburg, South Africa.
⁷ Department of Vascular Medicine and Haemostasis and Haemophilia Centre, University Hospitals Leuven, Leuven, Belgium.
⁸ Center for Rare Disease and Hemophilia, Taichung Veterans General Hospital, Taichung, Taiwan.
⁹ West Midlands Comprehensive Care Haemophilia Centre, Queen Elizabeth Hospital, Birmingham, UK.
¹⁰ Department of Haematology, Royal Adelaide Hospital, Adelaide, South Australia, Australia; University of Adelaide, Adelaide, South Australia, Australia.
¹¹ Hemophilia Treatment Center, University of California Davis, Sacramento, California, USA.
¹² Haemostasis & Thrombosis Unit, Haemophilia Treatment Centre, The Alfred Hospital, Melbourne, Victoria, Australia.
¹³ Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
¹⁴ Pediatric Hematology Oncology, Saint Joseph's Children's Hospital, Tampa, Florida, USA.
¹⁵ Department of Haematology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia.
¹⁶ AP-HM, Department of Pediatric Hematology Oncology, Children Hospital La Timone & Aix Marseille University, INSERM, INRA, C2VN, Marseille, France.
¹⁷ Complejo Hospitalario Universitario A Coruña, A Coruña, Spain.
¹⁸ Department of Haematology, Southampton University Hospital, Southampton, UK.
¹⁹ Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, USA.
²⁰ Institute for Policy Advancement Ltd, Washington, DC, USA; McMaster University, Hamilton, Ontario, Canada.
²¹ Comprehensive Care Haemophilia Treatment Center, Vivantes Klinikum im Friedrichshain, Berlin, Germany; Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Germany.
²² BioMarin Pharmaceuticals UK Ltd, London, UK.
²³ BioMarin Pharmaceutical Inc, Novato, California, USA.
²⁴ Departments of Pediatrics and Pathology, University of Michigan, Ann Arbor, Michigan, USA.

PMID: 37678546
DOI: 10.1016/j.jtha.2023.08.032

Abstract

Background: Severe hemophilia A (HA) negatively impacts health-related quality of life (HRQOL).

Objectives: We aimed to analyze HRQOL in adult men with severe HA without inhibitors after valoctocogene roxaparvovec gene transfer in the phase 3 trial GENEr8-1.

Methods: Participant-reported outcomes were the hemophilia-specific quality of life questionnaire for adults (Haemo-QOL-A), the EQ-5D-5L instrument, the Hemophilia Activities List (HAL), and the Work Productivity and Activity Impairment Questionnaire: Hemophilia Specific (WPAI+CIQ:HS). Participants completed the questionnaires at baseline and through 104 weeks postinfusion with 6 × 10¹³ vg/kg of valoctocogene roxaparvovec. Scores were analyzed per participant characteristics and outcomes.

Results: For 132 HIV-negative participants, mean change from baseline in Haemo-QOL-A Total Score met the anchor-based clinically important difference (CID: 5.5) by week 12; the mean (SD) increase was 7.0 (12.6) at week 104. At week 104, improvement in Consequences of Bleeding, Treatment Concern, Worry, and Role Functioning domain scores exceeded the CID (6). EQ-5D-5L Utility Index scores improved above the CID at week 52, but not at week 104. EQ-5D-5L visual analog scale and HAL scores increased from baseline to week 104. Participants reported less activity and work impairment at week 104 than baseline. Participants with problem joints had lower mean baseline Haemo-QOL-A Total and domain scores than those without them, but improved over 104 weeks, except for 11 participants with ≥3 problem joints. Participants with 0 bleeds during the baseline prophylaxis period reported Haemo-QOL-A score improvements above the CID, including in the Consequences of Bleeding domain.

Conclusion: Valoctocogene roxaparvovec provided clinically meaningful HRQOL improvement for men with severe HA.

Keywords: gene therapy; health-related quality of life; hemophilia A; patient-reported outcome; valoctocogene roxaparvovec.

Publication types

Clinical Trial, Phase III
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Hemophilia A* / diagnosis
Hemophilia A* / drug therapy
Hemophilia A* / genetics
Hemorrhage
Humans
Male
Quality of Life
Surveys and Questionnaires

Substances

Valoctocogene Roxaparvovec