OC 52.3 - Efficacy and Safety of Fidanacogene Elaparvovec in Adults with Moderately Severe or Severe Hemophilia B: Results from the Phase 3 BENEGENE-2 Gene Therapy Trial

Tuesday, June 27, 2023

11:15 – 11:30 ET

Room: 710B

Session Available As: On-Demand

Presenting Author(s)

Adam Cuker, MD, MS (he/him/his)

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

Co-Author(s)

HA

Hazzaa Alzahrani

Consultant
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 Hematology Oncology and Radiation Physics, Skane University Hospital, and Institution of Translational Medicine, Lund University, Malmö, Sweden
Malmö, Skane Lan, Sweden
LF

Laurent Frenzel

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

Olga Katsarou

Director
Blood Transfusion Centre, National Reference Centre for Congenital Bleeding Disorders, Laiko General Hospital
Athens, Attiki, Greece
KK

Kaan Kavakli

Medical Doctor
Department of Hematology, Ege University Children’s Hospital, Izmir, Turkey
Ege, Izmir, Turkey
Robert Klamroth, MD, PhD (he/him/his)

Priv. Doz. Dr. med.
Vivantes Klinikum im Friedrichshain, Clinic for Internal Medicine Angiology and Haemostaseology
Berlin, Berlin, Germany
Davide Matino, MD (he/him/his)

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

Amy Shapiro

Medical Director
Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA
Indianapolis, Indiana, United States
JW

Jiaan-Der Wang

Medical Doctor
Center for Rare Disease and Hemophilia, Taichung Veterans General Hospital
Taichung, Taichung, Taiwan (Republic of China)
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

Statistician
Pfizer Inc.
Cambridge, Massachusetts, United States
Jeremy Rupon, MD,PhD

Hematology Clinical Program Lead
Pfizer Inc.
Collegeville, Pennsylvania, United States

Background: Fidanacogene elaparvovec (PF-06838435, formerly SPK-9001) is an adeno-associated virus-based gene therapy vector transferring 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, open-label, single-arm trial that enrolled adult males with hemophilia B (FIX:C ≤2 IU/dL) who had 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. Other secondary endpoints included annualized FIX consumption, ABR of specific bleed types (eg, spontaneous), and frequency of target joint bleeds. Adverse events (AEs) were monitored. Participants provided written informed consent and the study was approved by the relevant regulatory/ethics committees.

Results: Forty-five participants (median [range] age, 29 [18, 62] years) were dosed with fidanacogene elaparvovec. Total ABR was reduced by 71% post-fidanacogene elaparvovec treatment vs prophylaxis (mean ABR, 1.3 vs 4.4; P< 0.0001; Table 1) and was stable over time (0.4 at Year 3; n=21). Mean FIX activity, measured by one-stage SynthASil, one-stage Actin-FSL, and chromogenic assays, is shown in Table 2. FIX activity remained relatively stable at Month 24 (Table 2). Data for other secondary efficacy endpoints are shown in Table 1. Twenty-eight participants (62%) received corticosteroids for presumed immune response. No deaths, infusion-related serious AEs, 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.

Learning Objectives:

Understand the findings of the BENEGENE-2 phase 3 gene therapy trial
Describe the efficacy and safety of fidanacogene elaparvovec in participants with moderately severe to severe hemophilia B in the BENEGENE-2 study
Understand the feasibility of low-dose gene therapy for patients with hemophilia B