title: Impact of long-term elosulfase alfa treatment on respiratory function in patients with Morquio A syndrome.
abstract: To present long-term respiratory function outcomes from an open-label, multi-center, phase 3 extension study (MOR-005) of elosulfase alfa enzyme replacement therapy (ERT) in patients with Morquio A syndrome.
  
  
  
  In part 1 of MOR-005, patients initially randomized to ERT in the 24-week pivotal study (MOR-004) remained on their regimen (2.0 mg/kg/week or every other week); placebo patients were re-randomized to one of the two regimens. During part 2, all patients received elosulfase alfa 2.0 mg/kg/week. Respiratory function was one of the efficacy endpoints evaluated in MOR-005. Change from MOR-004 baseline to 120 weeks of treatment for the combined population was determined and compared with results from untreated patients from a Morquio A natural history study (MorCAP).
  
  
  
  Maximum voluntary ventilation (MVV) improved up to week 72 and then stabilized; forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) increased continuously over 120 weeks. Mean increases in the modified per-protocol population was 9.2 % for FVC, 8.8 % for FEV1, and 6.1 % for MVV after 120 weeks. All patients ≤14 years showed respiratory improvements, presumably in part related to growth; however, these were greater in treated patients. For those >14 years, treated patients showed improvements, while deterioration occurred in untreated. Altogether, the improvements were significantly greater (P < 0.05) in treated patients.
  
  
  
  Long-term ERT is associated with sustained improvements in respiratory function in Morquio A. In younger patients (≤14 years), some improvement may be ascribed to growth. In older patients, other mechanisms, e.g., decreased glycosaminoglycan storage, are likely involved.
authors.affiliation: The Mark Holland Metabolic Unit, Salford Royal NHS Foundation Trust, Ladywell NW2- 2nd Floor Room 112 Salford, Manchester, M6 8HD, UK. cfya@sky.com.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Hendriksz
authors.affiliation: New York University School of Medicine, André Cournand Pulmonary Physiology Laboratory, Bellevue Hospital, New York, NY, USA.
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Berger
authors.affiliation: Azienda Ospedaliera San Gerardo, Monza, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Parini
authors.affiliation: King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
authors.forename: Moeenaldeen D
authors.initials: MD
authors.lastname: AlSayed
authors.affiliation: Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Julian
authors.initials: J
authors.lastname: Raiman
authors.affiliation: Med Genet Serv HCPA, Dep Genet UFRGS & INAGEMP, Porto Alegre, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: Montreal Children's Hospital, Montreal, QC, Canada.
authors.forename: John J
authors.initials: JJ
authors.lastname: Mitchell
authors.affiliation: Lurie Children's Hospital & NWU Feinberg, Chicago, IL, USA.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Burton
authors.affiliation: Hospital de Niños de Cordoba, Cordoba, Argentina.
authors.forename: Norberto
authors.initials: N
authors.lastname: Guelbert
authors.affiliation: Belfast City Hospital, Belfast, NI, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Stewart
authors.affiliation: Royal Free London NHS Foundation Trust & UC, London, UK.
authors.forename: Derralynn A
authors.initials: DA
authors.lastname: Hughes
authors.affiliation: BioMarin Pharmaceutical Inc., Novato, CA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Matousek
authors.affiliation: BioMarin Pharmaceutical Inc., Novato, CA, USA.
authors.forename: Elaina
authors.initials: E
authors.lastname: Jurecki
authors.affiliation: BioMarin Pharmaceutical Inc., Novato, CA, USA.
authors.forename: Celeste
authors.initials: C
authors.lastname: Decker
authors.affiliation: UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Harmatz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002811:Chondroitinsulfatases / Q000627:therapeutic use*; D004311:Double-Blind Method; D056947:Enzyme Replacement Therapy / Q000379:methods; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects*; D006801:Humans; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D009085:Mucopolysaccharidosis IV / Q000188:drug therapy*; D012119:Respiration / Q000187:drug effects*; D012129:Respiratory Function Tests / Q000379:methods; D055815:Young Adult
chemical_list: D002811:Chondroitinsulfatases; C102295:GALNS protein, human