Health-Related Quality of Life Following Valoctocogene Roxaparvovec Gene Therapy for Severe Hemophilia A in the Phase 3 Trial GENEr8-1

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.4916-4916
• Main Authors: O'Mahony, Brian, Mahlangu, Johnny, Peerlinck, Kathelijne, Wang, Jiaan-Der, Lowe, Gillian, Tan, Chee Wee, Giermasz, Adam, Tran, Huyen A, Khoo, Teh-Liane, Cockrell, Erin, Pepperell, Dominic, Chambost, Hervé, López Fernández, María Fernanda, Kazmi, Rashid, Majerus, Elaine, Skinner, Mark W, Klamroth, Robert, Quinn, Jennifer, Yu, Hua, Wong, Wing Yen, Lawal, Adebayo, Robinson, Tara M, Kim, Benjamin
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-146021

Introduction. Severe hemophilia A (HA) negatively impacts health-related quality of life (HRQOL) through joint pain and disability, treatment burden, and effects on mental and emotional health; chronic pain and mental health are core outcomes for hemophilia gene therapy trials (Iorio, et al. Haemophilia 2018;24[4]:e167-72). In the phase 3 trial GENEr8-1 (NCT03370913), men with severe HA who received valoctocogene roxaparvovec (AAV5-hFVIII-SQ) gene therapy experienced a significant increase in endogenous FVIII activity that resulted in reduced bleeding events and FVIII utilization from baseline through 52 weeks (Ozelo, et al. Res Pract Thromb Haemost 2021;5). Here, we analyzed the impact of valoctocogene roxaparvovec on HRQOL. Methods. Men ≥18 years of age with FVIII ≤1 IU/dL previously receiving standard-of-care FVIII prophylaxis and without history of FVIII inhibitors received one 6x10 13 vg/kg valoctocogene roxaparvovec infusion. This analysis included HIV-negative participants who completed the weeks 49-52 visit. Participants completed QOL questionnaires at baseline and weeks 4, 12, 26, and 52 post-gene therapy infusion. Change from baseline was assessed with a two-sided t-test without multiplicity control. Missing data were not imputed. Measures included the hemophilia-specific Haemo-QOL-A questionnaire, which consists of 6 domain scores (Physical Functioning, Role Functioning, Consequences of Bleeding, Worry, Emotional Impact, Treatment Concern) and Total Score ranging from 0-100 (Rentz, et al. Haemophilia 2008;14[5]:1023-34); and the EQ-5D-5L, a general measure of HRQOL that assesses functional dimensions (Mobility, Self-Care, Usual Activities) as well as Pain/Discomfort and Anxiety/Depression (Herdman, et al. Qual Life Res 2011;20[10]:1727-36). EQ-5D-5L results are reported as visual analog scale (VAS; range, 0-100) and Utility Index Score (range, 0-1), which is calculated from population norms (Janssen, et al. Qual Life Res 2013;22[7]:171-27). Higher scores indicate better HRQOL. The anchor-based clinically important differences (CID) used for the Haemo-QOL-A were 5.5 for Total Score and 6 for domain scores (Quinn, et al. Abstract, Hemophilia Federation of America Virtual Conference, Aug 2020). For the EQ-5D-5L Index, 0.03 was considered a CID (Kaplan. COPD 2005;2[1]:91-7). However, use of general population norms, together with the presence of a disability paradox in hemophilia, causes the EQ-5D-5L to underestimate the negative impact of hemophili