OC 30.5 - Efficacy and safety of fidanacogene elaparvovec in adults with moderately severe or severe hemophilia B: updated results from the phase 3 BENEGENE-2 gene therapy trial

Monday, June 24, 2024

10:30 – 10:45 ICT

Room: Plenary Hall

Co-Author(s)

JW

Jiaan-Der Wang, PhD

Director
Center for Rare Disease and Hemophilia, Department of Pediatrics, Taichung Veterans General Hospital
Taichung, Taichung, Taiwan (Republic of China)

Co-Author(s)

Adam Cuker, MD, MS

Department of Medicine and Department of Pathology and Laboratory Medicine
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Philadelphia, Pennsylvania, United States
HA

Hazzaa Alzahrani

Adult Haematology
King Faisal Specialist Hospital and Research Centre Riyadh, Saudi Arabia
Riyadh, Ar Riyad, Saudi Arabia
JA

Jan Astermark

Professor, Senior Consultant
Department of Translational Medicine, Lund University, Malmö, Sweden
Malmo, Skane Lan, Sweden
LF

Laurent Frenzel

Department of Haematology
Institut Necker, Paris, France
Paris, Ile-de-France, France
OK

Olga Katsarou

Head of the Blood Transfusion Unit, Laiko hospital, Greece
Laiko Hospital, Blood Transfusion Centre, National Reference Centre for Congenital Bleeding Disorders, Athens, Greece
Athens, Attiki, Greece

Presenting Author(s)

Kaan Kavakli, MD

Division of Hematology, Department of Pediatrics
Ege University Faculty of Medicine, Turkey
Ege, Izmir, Turkey

Co-Author(s)

Robert Klamroth, MD

Head of Department
Vivantes Klinikum, Friedrichshain, Berlin, Germany
Berlin, Berlin, Germany
Davide Matino

Assistant Professor
Division of Hematology & Thromboembolism, Department of Medicine, McMaster University, Ontario, Canada
Hamilton, Ontario, Canada
AS

Amy D Shapiro

Indiana Hemophilia & Thrombosis Center, Inc.
Indianapolis, IN, USA
Indianapolis, Indiana, United States
MK

Matco Kalac

Category Clinician, Sr. Director
Pfizer Inc.
Collegeville, Pennsylvania, United States
JF

Joanne Fuiman

Director, Study Clinician
Pfizer Inc.
Collegeville, Pennsylvania, United States
JM

John McKay

Senior Director
Pfizer Inc.
Groton, Connecticut, United States
PS

Pengling Sun

Director, Research Statistics
Pfizer Inc.
Cambridge, Massachusetts, United States
Jeremy Rupon

Clinical Group Lead
Pfizer Inc.
Collegeville, Pennsylvania, United States
FP

Frank Plonski

Global Clinical Lead, Pfizer Research and Development
Pfizer Inc
Collegeville, Pennsylvania, United States

Background: Fidanacogene elaparvovec, an adeno-associated virus-based gene therapy, transfers the high-activity variant of human factor IX (FIX) FIX-R338L for the treatment of hemophilia B.

Aims: To evaluate the efficacy and safety of fidanacogene elaparvovec in participants with moderately severe or severe hemophilia B.

Methods: BENEGENE-2 (NCT03861273) is a phase 3 trial that enrolled adult males with hemophilia B (FIX:C ≤2%) who completed ≥6 months of FIX prophylaxis prior to administration of 5e11 vg/kg fidanacogene elaparvovec. The primary endpoint was non-inferiority on annualized bleeding rate (ABR) for total (treated and untreated) bleeds from Week 12 to Month 15 post-infusion vs the pre-infusion prophylaxis period. Key secondary endpoints included FIX activity, ABR for treated bleeds, and annualized infusion rate. Participants provided written informed consent and the study was approved by the relevant regulatory/ethics committees. This study was sponsored by Pfizer.

Results: Forty-five participants (median [range] age, 29 [18–62] years) were dosed with fidanacogene elaparvovec 5e11 vg/kg. As of August 2023, 44 participants completed ≥15 months follow-up (up to 4.0 years); the 45th participant had >12 months follow-up; we previously reported on 41 with ≥15 months of follow-up). Total ABR was reduced by 71% from Week 12 to Month 15 post-gene therapy vs prophylaxis (mean ABR, 1.3 vs 4.4; P< 0.0001; Table 1). Mean FIX activity measured by one-stage SynthASil, one-stage Actin-FSL, and chromogenic assays is shown in Table 2. FIX activity remained stable at Month 24 in 39 participants (as measured by SynthASil assay) (Table 2). Secondary efficacy endpoints are reported in Table 1. Twenty-eight (62%) participants received corticosteroids for presumed immune response. No deaths, infusion-related serious adverse events, thrombotic events, or FIX inhibitors were reported.

Conclusion(s): Fidanacogene elaparvovec yielded endogenous FIX expression in participants with moderately severe to severe hemophilia B, resulting in significant decreases in bleeding, and was generally well tolerated.