PB0558 - Efficacy, Safety and Quality of Life Three Years After Gene Transfer With Valoctocogene Roxaparvovec in a Brazilian Cohort

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Margareth C. Ozelo, MD, PhD

Professor
Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas
Campinas, Sao Paulo, Brazil

Co-Author(s)

Gabriela G. Yamaguti-Hayakawa

Hematologist
Hemocentro Unicamp, Universidade de Campinas (Unicamp), Campinas, SP, Brasil
Campinas, Sao Paulo, Brazil
Alessandra Nunes Loureiro Prezotti, MD, MsC, PhD

Hematologist
HEMOES - Centro de Hemoterapia e Hematologia do Espírito Santo
Vitória, Espirito Santo, Brazil
MC

Monica Cerqueira

Hematologist
Hemocentro do Estado do Rio de Janeiro (HEMORIO), Rio de Janeiro, RJ, Brasil
Rio de Janeiro, Rio de Janeiro, Brazil
PV

Paula Villaça

Hematologist
Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, São Paulo, Brazil
São Paulo, Sao Paulo, Brazil
CL

Claudia Santos Lorenzato

Hematologist
Centro de Hematologia e Hemoterapia do Paraná (Hemepar), Curitiba, PR, Brasil
Rio de Janeiro, Parana, Brazil
TR

Tara M. Robinson

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

Background: Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) provides endogenous factor VIII (FVIII) production in people with severe hemophilia A. In the multicenter, phase 3 GENEr8-1 study (NCT03370913), participants who received 6x10e13 vg/kg valoctocogene roxaparvovec achieved FVIII activity that provided improved protection from bleeds compared with FVIII prophylaxis over 156 weeks (W) along with improvements in quality of life (QoL) and stable safety profile.

Aims: To evaluate bleeding rate, FVIII utilization, corticosteroid use, quality of life and safety outcomes after 3 years post-gene transfer in the Brazilian cohort.

Methods: The GENEr8-1 trial evaluated 6x1013 vg/kg valoctocogene roxaparvovec in 134 men with severe hemophilia A (FVIII ≤1 IU/dL) of which 18 were from Brazil (19 patients were originally enrolled from Brazilian but one patient left the country and is currently followed up in a study center in Spain). Bleeds and FVIII use were self-reported after regular prophylaxis ended (scheduled for W4) through data cutoff and comparisons to baseline on were performed. QoL per Haemo-QoL-A and EQ-5D-5L, corticosteroid utilization and safety were assessed.

Results: Eighteen participants (mean [SD] age, 28.33 [6.77]; mean [SD] weight, 81.21 [19.37]) completed W156. At Year-3, ABR (treated) was 0.4 (Table 1). Mean (SD) HEMO-QoL-A improvement from baseline exceeding the anchor-based clinically important difference (5.5) (Year-1, 7.44±11.38, Year-2, 8.98±12.64; Year-3, 8.53±9.96). Additional data for bleeds, adverse events and corticosteroid use are presented in Table 1, and annualized FVIII utilization and QoL over 3 years of follow-up post-treatment with valoctocogene roxaparvovec are presented in Table 2.

Conclusion(s): Valoctocogene roxaparvovec provided robust hemostatic efficacy relative to FVIII prophylaxis for 3 years, with QoL improvement and stable safety profile in Brazilian patients.