Brazilian Experience with Delandistrogene moxeparvovec in Duchenne Muscular Dystrophy

Topic:

Clinical Management

Poster Number: 40 S

Author(s):

FELIPE FRANCO DA GRACA, MD, Universidade Estadual de Campinas (UNICAMP), Michele Michelin Becker, MD PHD, Hospital de Clínicas de Porto Alegre, Cristina Iwabe, PhD, Universidade Estadual de Campinas (UNICAMP), Clara Gontijo Camelo, MD, PhD, University of Sao Paulo, Giovana Barros e Silva Ribeiro, MD, Universidade Estadual de Campinas (UNICAMP), Tania Virginia Fernandes Silva, MD, HCB Hospital da Criança de Brasília José Alencar, Janaina Monteiro Chaves, MD, HCB Hospital da Criança de Brasília José Alencar, Leonardo Simao Medeiros, MD PhD, Hospital de Clínicas de Porto Alegre, Livia Lobo da Silva Costa Henrique, MD, Livia Lobo Neurologia Infantil, Juan Llerena Jr, MD PhD, IFF Fiocruz, Luiz Fernando Grossklauss, MD, Universidade Federal de São Paulo (UNIFESP), Adriana Banzzato Ortega, MD, Hospital Pequeno Príncipe Curitiba, Andre Pesssoa, MD PhD, Universidade Federal do Ceará, Jonas Saute, MD PhD, Hospital de Clínicas de Porto Alegre, Marcondes Cavalcante França Jr, MD PhD, Universidade Estadual de Campinas (UNICAMP)

Background:
Duchenne muscular dystrophy (DMD) is a severe X-linked disorder caused by mutations in the DMD gene. Delandistrogene moxeparvovec (DM) is an AAVRh74-based gene therapy delivering a shortened micro-dystrophin gene. We report the initial Brazilian experience with anti-AAVRh74 antibody testing and clinical outcomes in treated patients.
Methods:
A total of 117 patients with genetically confirmed DMD underwent anti-AAVRh74 antibody testing (mean age 6.5 years). Seropositivity distribution and post-treatment outcomes were analyzed. Patients eligible for infusion were antibody-negative and had no deletions involving exons 8 or 9.
Results:
Anti-AAVRh74 antibodies were detected in 29 of 117 patients (24.8%). Fourteen positive patients were retested after ≥1 month, all remaining positive. Two regional clusters of high seropositivity were identified: 10/17 in Paraná (58.8%) in southern Brazil and 4/9 in Ceará (44.4%) in northeastern Brazil. Fifteen antibody-negative patients (ages 5–8 years) received DM. Follow-up ranged from 2 to 19 months. No infusion-related reactions occurred. One patient developed a transient systemic inflammatory response 48 hours post-infusion and later, seven months after infusion, an immune-mediated myositis currently under treatment. One patient died three months post-infusion from influenza-related ARDS; a causal link with therapy was considered uncertain. Three others showed transient transaminase elevations managed with corticosteroid adjustment. Among patients with ≥6 months follow-up (excluding the myositis case), mean NSAA improvement was +4.5 points, with faster timed tests performances. There was MRI evidence of increased lower limb muscle volume in one of three evaluated cases after just 3 months of the infusion.
Conclusions:
This early Brazilian experience indicates a relevant rate of anti-AAVRh74 seropositivity, with regional clustering. In antibody-negative patients, DM showed functional and imaging improvements. However, close and continued monitoring in specialized centers is essential due to the potential for emerging and serious adverse effects.