PB0229 - Results from the Taiwanese cohort in GENEr8-1: bleeding rates, factor VIII usage, quality of life and safety in severe Hemophilia A patients after gene therapy

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Sheng-Chieh Chou, MD.

Hematologist
Department of Internal Medicine, National Taiwan University Hospital
Taipei, Taipei, Taiwan (Republic of China)

Co-Author(s)

Shyh-Shin Chiou, MD, PhD

President/Professor/Director/Doctor
Division of Pediatric Hematology and Oncology, Kaohsiung Medical University Hospital
Kaohsiung, Kaohsiung, Taiwan (Republic of China)
Yeu-Chin Chen, MD

Associate Professor/Doctor, Director of hemophilia care & research center
Division of Hematology/Oncology, Tri-Service General Hospital, Defense Medical Center
Taipei, Taipei, Taiwan (Republic of China)
SS

Sandra Santos

Director
BioMarin Pharmaceuticals Inc.
Novato, California, United States
TR

Tara M. Robinson

Senior Medical Director
BioMarin Pharmaceuticals Inc.
Novato, California, United States
MS

Ming-Ching Shen

Haematologist
Division of Hematology-Oncology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 50046, Taiwan
Changhua, Taipei, Taiwan (Republic of China)

Background: Valoctocogene roxaparvovec enables endogenous FVIII production to prevent bleeding in people with severe hemophilia A. In the phase 3 GENEr8-1 study, valoctocogene roxaparvovec showed improved annualized bleeding rate (ABR) compared with FVIII prophylaxis over the efficacy evaluation period (EEP) followed by reduction in annualized FVIII usage (AFU) and infusion rates (AFR), and improvements in quality of life (QOL).

Aims: Evaluate outcomes after 3 years post-gene transfer in the Taiwanese cohort included in GENEr8-1 study.

Methods: GENEr8-1 trial evaluated a single 6×1013 vg/kg valoctocogene roxaparvovec infusion in adult men with severe hemophilia A without inhibitors. Bleeds and FVIII use were self-reported after regular prophylaxis ended through end of follow-up and changes from baseline during the EEP (from week 5 post dosing (Study Day 33) or 3 days after the end of FVIII prophylaxis, whichever was later, to the last visit by the data cutoff date) were assessed. QOL per EQ-5D-5L and safety were also assessed.

Results: GENEr8-1 enrolled 10 participants in Taiwan with a median follow-up post-infusion of 158 weeks.). Demographics and baseline disease characteristics are described in Table 1.
During the EEP, the mean treated ABRwas reduced in 94% from baseline to 0.50 bleeds/year, mean AFU and AFR were reduced in 98.2% to 62.61 IU/kg/year and 1.69 infusions per Year, respectively (Table 2). None of the participants resumed prophylaxis. At week 156, the mean (median) FVIII activity level by chromogenic assay was 19.78 (13.98) IU/dL. Mean (95%CI) EQ-5D-5L Index Score improvement from baseline (0.84) to W52 was 0.09 (-0.01, 0.19), to W104 was 0.10 (-0.03, 0.22) and to W156 was 0.06 (-0.08, 0.20). 3/10 experienced Grade ≥ 3 adverse events.

Conclusion(s): In Taiwanese patients, valoctocogene roxaparvovec provided robust hemostatic efficacy relative to FVIII prophylaxis for more than 3 years, with improvements in QOL and stable safety.