Long-term follow-up of endurance and safety outcomes during enzyme replacement therapy for mucopolysaccharidosis VI: Final results of three clinical studies of recombinant human N-acetylgalactosamine 4-sulfatase.
The objective of this study was to evaluate the long-term clinical benefits and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome), a lysosomal storage disease. Fifty-six patients derived from 3 clinical studies were followed in open-label extension studies for a total period of 97-260 Weeks. All patients received weekly infusions of rhASB at 1 mg/kg. Efficacy was evaluated by (1) distance walked in a 12-minute walk test (12MWT) or 6-minute walk test (6MWT), (2) stairs climbed in the 3-minute stair climb (3MSC), and (3) reduction in urinary glycosaminoglycans (GAG). Safety was evaluated by compliance, adverse event (AE) reporting and adherence to treatment.


RESULTS
A significant reduction in urinary GAG (71-79%) was sustained. For the 12MWT, subjects in Phase 2 showed improvement of 255+/-191 m (mean+/-SD) at Week 144; those in Phase 3 Extension demonstrated improvement from study baseline of 183+/-26 m (mean+/- SE) in the rhASB/rhASB group at Week 96 and from treatment baseline (Week 24) of 117+/-25 m in the placebo/rhASB group. The Phase 1/2 6MWT and the 3MSC from Phase 2 and 3 also showed sustained improvements through the final study measurements. Compliance was 98% overall. Only 560 of 4121 reported AEs (14%) were related to treatment with only 10 of 560 (2%) described as severe.


CONCLUSIONS
rhASB treatment up to 5 years results in sustained improvements in endurance and has an acceptable safety profile.
Harmatz
Paul
P
Children's Hospital & Research Center Oakland, 747 52nd Street, Oakland, CA 94609, USA.
Giugliani
Roberto
R
Serviço de Genética Médica/HCPA and Department of Genetics/UFRGS, Porto Alegre, Brazil.
D Schwartz
Ida Vanessa
IV
Serviço de Genética Médica/HCPA and Department of Genetics/UFRGS, Porto Alegre, Brazil.
Guffon
Nathalie
N
Hôpital Edouard Herriot Pavillon S, Maladies Metaboliques, Lyon, France.
Teles
Elisa Leão
EL
Unidade de Doenças Metabólicas, Departamento Pediatria, Hospital de Sao João, Porto, Portugal.
Miranda
M Clara Sá
MCS
Unidade de Biologia do Lisossoma e Peroxisoma, Instituto de Biologia Molecular e Celular, Porto, Portugal.
Wraith
J Edmond
JE
Royal Manchester Children's Hospital, Manchester, UK.
Beck
Michael
M
Children's Hospital, University of Mainz, Germany.
Arash
Laila
L
Children's Hospital, University of Mainz, Germany.
Scarpa
Maurizio
M
Department of Pediatrics, University of Padova, Padova, Italy.
Ketteridge
David
D
Department of Genetic Medicine, Women's and Children's Hospital Adelaide, North Adelaide, Australia.
Hopwood
John J
JJ
Department of Genetic Medicine, Women's and Children's Hospital Adelaide, North Adelaide, Australia.
Plecko
Barbara
B
Univ. Klinik fur Kinder und Jugendheilkunde, Graz, Austria.
Steiner
Robert
R
Departments of Pediatrics and Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA.
Whitley
Chester B
CB
University of Minnesota Medical School, Minneapolis, MN, USA.
Kaplan
Paige
P
Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Yu
Zi-Fan
ZF
Statistics Collaborative, Inc., Washington, DC, USA.
Swiedler
Stuart J
SJ
BioMarin Pharmaceutical Inc, Novato, CA, USA.
Decker
Celeste
C
BioMarin Pharmaceutical Inc, Novato, CA, USA.
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D008297:Male; D009043:Motor Activity; D009087:Mucopolysaccharidosis VI / Q000503:physiopathology / Q000628:therapy*; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D016138:Walking
D006025:Glycosaminoglycans; D011994:Recombinant Proteins; D020051:N-Acetylgalactosamine-4-Sulfatase