OC 20.3 - Improved Joint Health After Gene Therapy with Dirloctocogene Samoparvovec (SPK-8011) in People with Hemophilia A

Sunday, June 25, 2023

15:15 – 15:30 ET

Room: 517

Session Available As: Live-Stream and On-Demand

Presenting Author(s)

Benjamin J. Samelson-Jones, PhD, MD

Assistant Professor of Pediatrics
Division of Hematology and the Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania, United States

Co-Author(s)

Margaret V. Ragni, MD, MPH (she/her/hers)

Professor of Medicine and Clinical and Translational Science
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
Pittsburgh, Pennsylvania, United States
JR

John E.J. Rasko

Head of Department
Department of Cell and Molecular Therapies, Royal Prince Alfred Hospital, and the Gene and Stem Cell Therapy Program, Centenary Institute, Faculty of Medicine and Health, University of Sydney
Camperdown, New South Wales, Australia
KH

Kristina M. Haley

Associate Professor of Pediatrics
Department of Pediatrics, Oregon Health & Science University
Portland, Oregon, United States
SC

Stacy E. Croteau

Assistant Professor of Pediatrics
Department of Pediatrics, Harvard Medical School, and the Division of Hematology and Oncology, Boston Children’s Hospital
Boston, Massachusetts, United States
Jerome Teitel, MD

Professor
St Michael's Hospital Haemophilia Treatment Centre, University of Toronto
Toronto, Ontario, Canada
HT

Huyen Tran

Professor
Australian Centre for Blood Diseases, Monash University
Melbourne, Victoria, Australia
PC

Peter H. Cygan

Assistant Professor of Medicine
Department of Medicine, Division of Blood and Vascular Disorders, Penn State Health Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States
SS

Spencer Sullivan

Chief Executive Officer, Hematology
Mississippi Center for Advanced Medicine
Madison, Mississippi, United States
JM

Jill Moormeier

Professor - Department of Internal Medicine
Department of Medicine, UMKC School of Medicine
Kansas City, Missouri, United States
SJ

Savina Jaeger

Head of Biostatistics
Spark Therapeutics, Inc.
Philadelphia, Pennsylvania, United States
AL

Alex Long

Senior Biostatician
Spark Therapeutics, Inc.
Philadelphia, Pennsylvania, United States
GL

Gallia Levy

Chief Medical and Product Strategy Officer
Spark Therapeutics, Inc.
Philadelphia, Pennsylvania, United States
AM

Amy MacDougall

Clinical Development Lead
Spark Therapeutics, Inc.
Philadelphia, Pennsylvania, United States
KJ

Kristen Jaworski

Clinical Trial Liaison
Spark Therapeutics, Inc.
Philadelphia, Pennsylvania, United States
TC

Tiffany Chang

Clinical Development Lead
Spark Therapeutics, Inc.
Philadelphia, Pennsylvania, United States

Background: Joint health preservation in hemophilia A (HA) remains a concern despite prophylaxis advancements. Dirloctocogene samoparvovec (SPK-8011), an investigational adeno-associated viral vector gene therapy for HA, demonstrated a 92% (95% CI: 89–94%) reduction in annualized bleed rate in a Phase I/II trial. Before enrollment, 72% of participants were receiving factor (F)VIII prophylaxis.

Aims: To report impact on joints for participants who received dirloctocogene samoparvovec.

Methods: In this open-label, multicenter, non-randomized dose-escalation trial with a long-term extension (NCT03003533/NCT03432520; funded by Spark Therapeutics), males with FVIII activity ≤2% received dirloctocogene samoparvovec (George, et al. NEJM 2021). Informed consent and ethics approvals were obtained. Joint health was assessed using the Hemophilia Joint Health Score (HJHS) v2.1. Presence and resolution of target joints were recorded according to ISTH definitions. Impact on self-perceived function was assessed using the Hemophilia Activities List (HAL) questionnaire.

Results: Participants with baseline and Year 1 data were included. Two participants who lost transgene expression were excluded. By data cut-off (Oct 4, 2022), mean total HJHS had improved at Years 1–3; change from baseline was clinically meaningful at Years 2 and 3 (Fig. 1). Some HJHS components showed improvements, with proportions of participants with severe symptoms decreasing over time (Fig. 2 shows left elbow assessment). Seven participants had target joints in the year before receiving dirloctocogene samoparvovec; each resolved by Year 1. Participants’ self-perceived function in mean (standard deviation [SD]) ‘Leisure activities and sports’ score (HAL) changed from 85.6 (15.6) before dirloctocogene samoparvovec to 98.7 (2.1) at Year 1 (n=15); improvement was maintained through Year 3. No participant with sustained transgene expression resumed FVIII prophylaxis.

Conclusion(s): Clinically meaningful improvements in joint health, ongoing at Year 3, were observed in participants receiving dirloctocogene samoparvovec, suggesting that this treatment may reduce the pain and musculoskeletal restrictions of HA. Improvement in participants’ self-reported function corroborated these results.

Learning Objectives:

Understand the potential of dirloctocogene samoparvovec to clinically improve the joint health of hemophia recipients.
Understand that the trend of improving joint health was observed in hemophilia A recipients previously on prophylaxis and on-demand therapy.
Describe the benefit of dirloctocogene samoparvovec for resolving target joints.