Disease characteristics, effectiveness, and safety of vestronidase alfa for the treatment of patients with mucopolysaccharidosis VII in a novel, longitudinal, multicenter disease monitoring program.

Autor: Giugliani R; Dep Genetics UFRGS, Casa dos Raros, INAGEMP, Med Genet Serv HCPA, and DASA Genomics, Porto Alegre, Brazil. rgiugliani@hcpa.edu.br., Gonzalez-Meneses A; Hospital Universitario Virgen del Rocio, Seville, Spain., Scarpa M; Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, Udine, Italy., Burton B; Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Wang R; University of California Irvine School of Medicine, Children's Health of Orange County, Orange, CA, USA., Martins E; Centro Hospitalar Universitário de Santo António, Porto, Portugal., Oussoren E; Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands., Hennermann JB; University Medical Center Mainz, Villa Metabolica, Mainz, Germany., Chabrol B; Centre Hospitalier Universitaire La Timone, Marseille, France., Grant CL; Children's National Hospital, Washington, District of Columbia, USA., Sun A; Seattle Children's Hospital, Seattle, WA, USA., Durand C; Laboratorio Chamoles, Buenos Aires, Argentina., Hetzer J; Ultragenyx Pharmaceutical Inc, Novato, CA, USA., Malkus B; Ultragenyx Pharmaceutical Inc, Novato, CA, USA., Marsden D; Ultragenyx Pharmaceutical Inc, Novato, CA, USA., Merritt Ii JL; Ultragenyx Pharmaceutical Inc, Novato, CA, USA.
Jazyk: angličtina
Zdroj: Orphanet journal of rare diseases [Orphanet J Rare Dis] 2024 May 07; Vol. 19 (1), pp. 189. Date of Electronic Publication: 2024 May 07.
DOI: 10.1186/s13023-024-03176-z
Abstrakt: Background: Mucopolysaccharidosis VII (MPS VII) is an ultra-rare, autosomal recessive, debilitating, progressive lysosomal storage disease caused by reduced activity of β-glucuronidase (GUS) enzyme. Vestronidase alfa (recombinant human GUS) intravenous enzyme replacement therapy is an approved treatment for patients with MPS VII.
Methods: This disease monitoring program (DMP) is an ongoing, multicenter observational study collecting standardized real-world data from patients with MPS VII (N ≈ 50 planned) treated with vestronidase alfa or any other management approach. Data are monitored and recorded in compliance with Good Clinical Practice guidelines and planned interim analyses of captured data are performed annually. Here we summarize the safety and efficacy outcomes as of 17 November 2022.
Results: As of the data cutoff date, 35 patients were enrolled: 28 in the Treated Group and seven in the Untreated Group. Mean (SD) age at MPS VII diagnosis was 4.5 (4.0) years (range, 0.0 to 12.4 years), and mean (SD) age at DMP enrollment was 13.9 (11.1) years (range, 1.5 to 50.2 years). Ten patients (29%) had a history of nonimmune hydrops fetalis. In the 23 patients who initiated treatment prior to DMP enrollment, substantial changes in mean excretion from initial baseline to DMP enrollment were observed for the three urinary glycosaminoglycans (uGAGs): dermatan sulfate (DS), -84%; chondroitin sulfate (CS), -55%; heparan sulfate (HS), -42%. Also in this group, mean reduction from initial baseline to months 6, 12, and 24 were maintained for uGAG DS (-84%, -87%, -89%, respectively), CS (-70%, -71%, -76%, respectively), and HS (+ 3%, -32%, and - 41%, respectively). All adverse events (AEs) were consistent with the known vestronidase alfa safety profile. No patients discontinued vestronidase alfa. One patient died.
Conclusions: To date, the DMP has collected invaluable MPS VII disease characteristic data. The benefit-risk profile of vestronidase alfa remains unchanged and favorable for its use in the treatment of pediatric and adult patients with MPS VII. Reductions in DS and CS uGAG demonstrate effectiveness of vestronidase alfa to Month 24. Enrollment is ongoing.
(© 2024. The Author(s).)
Databáze: MEDLINE
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