Skinner M, Chen E, Ibrahim Q, Kucher A, Germini F, Karimi M, Clearfield E , O’Mahony B , Jain M. Gene Therapy in Hemophilia A: the Impact of Valoctocogene Roxaparvovec on Patient Outcomes – Initial Results from Patient Reported Outcomes, Burdens and Experiences (PROBE) from the GENEr8-1 Trial. (Abstract). NHF (2023).
Objective
The Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire is included in the phase 3, open-label, single-arm study (GENEr8-1) as a tertiary endpoint. The aim is to assess the effect of a single intravenous administration of valoctocogene roxaparvovec on patient-reported health and life experiences using PROBE.
Methods
134 adult men with FVIII ≤1 IU/dL without history of FVIII inhibitors and AAV5 antibodies previously receiving FVIII prophylaxis were enrolled in the GENEr8-1 trial for hemophilia A. Results from baseline, week 52 and week 104 were summarized. The PROBE questionnaire comprises four sections: demographics, general health problems, hemophilia-specific problems, and health-related quality of life (HRQoL) with the 5-level EQ-5D tool. While further validation to understand the performance of PROBE in this context of use is ongoing, this study summarized the initial PROBE summary score results (based on section 2) utilizing existing scoring algorithms. Change from baseline summary score was assessed with paired t-tests.
Summary
PROBE score was available for 124/134 (93%) at baseline, 129/132 (98%) at week 52, and 129/130 (99%) at week 104. Mean PROBE scores (SDs) were 0.82 (0.13), 0.87 (0.12) and 0.86 (0.13) at the baseline, week 52 and week 104 respectively. Average changes in score of 0.05 [95% CI: (0.03, 0.07), p <0.001] and 0.05 (0.02, 0.07), p<0.001) were observed at weeks 52 and 104. Item-level analyses suggested fewer participants reported pain, limitations in activities of daily living, and target joints at weeks 52 and 104 vs. baseline. Two years after treatment, the percentage of participants working full-time increased by >10% (Table 1). Overall, these results were consistent with EQ-5D results (Table 2).
Conclusions
Valoctocogene roxaparvovec led to measurable changes in HRQoL 2 years after a single administration. Further research is necessary to interpret clinically meaningful change in PROBE scores.
Disclosures
Er Chen: Bio Marin Pharmaceutical Inc.; Federico Germini: Bayer Bio Marin Pharmaceutical Inc., Novo Nordisk, Pfizer, Roche, Takeda; Mohit Jain: Bio Marin Pharmaceutical Inc.; Milad Karimi: Bio Marin Pharmaceutical Inc.;
Brian O’Mahony BioMarin Pharmaceutical Inc.CSL Behring; Mark Skinner: Bayer, Bio Marin Pharmaceutical Inc., Blue Cross Blue Shield, ICERMASACNHFNORD, Novo Nordisk, Pfizer, Roche/Genentech, Spark, Takeda, WFH, USA
Poster: HERE
