OC 20.2 - 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

Sunday, June 25, 2023

15:00 – 15:15 ET

Room: 517

Session Available As: Live-Stream and On-Demand

Presenting Author(s)

Mark W. Skinner, JD (he/him/his)

President and CEO
Institute for Policy Advancement Ltd.
Washington, District of Columbia, United States

Co-Author(s)

EC

Er Chen

Director, Global Value & Access Lead Roctavian
BioMarin Pharmaceuticals Inc.
Novato, California, United States
QI

Quazi Ibrahim

Statistician
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON
Hamilton, Ontario, Canada
AK

Alexandra Kucher

Research Data Manager
Patient Outcomes Research Group Ltd
Washington DC, District of Columbia, United States
Federico Germini, MD, MSc, PhD

Assistant Professor
Department of Medicine, McMaster University, Hamilton, ON
Hamilton, Ontario, Canada
MK

Milad Karimi

Associate Director, Patient and Health Outcomes
BioMarin Pharmaceuticals Inc.
Novato, California, United States
EC

Elizabeth Clearfield

Senior Research Manager
Institute for Policy Advancement Ltd.
Baltimore, Maryland, United States
Brian O'Mahony

CEO
Irish Hemophilia Society
Dublin, Dublin, Ireland
MJ

Mohit Jain

VP, Value, Access and Strategic Pricing, Global Head
BioMarin Pharmaceuticals Inc.
Novato, California, United States

Background: 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.

Aims: 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.

Results: 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).

Conclusion(s): 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.

Learning Objectives:

Understand application of a novel, hemophilia-specific patient-reported outcome measure in a phase 3 gene therapy clinical trial
Understand the effect of a one-time infusion of valoctocogene roxaparvovec on health outcomes, burdens and experiencs identified as important by people living with hemophilia
Understand the future direction for generation of real world evidence using patient-centered outcomes with novel hemophilia treatments