title: Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study.
abstract: Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), and two patients missed >20% of planned infusions; 10 completed treatment through 48 weeks and received ≥80% of planned infusions (Modified Per Protocol [MPP] population). The study population had more advanced disease than that enrolled in other trials. From baseline to week 48, MPP data showed biochemical efficacy (urine KS decreased 52.4%). The remaining efficacy results were highly variable due to challenges in test execution because of severe skeletal and joint abnormalities, small sample sizes, and clinical heterogeneity among patients. Eight patients showed improvements in one or more outcome measures; several patients indicated improvements not captured by the study assessments (e.g., increased energy, functional ability). The nature of adverse events was similar to other elosulfase alfa studies. This study illustrates the considerable challenges in objectively measuring impact of ERT in very disabled Morquio A patients and highlights the need to examine results on an individual basis. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.
authors: UCSF Benioff Children's Hospital Oakland, Oakland, California.
authors: Paul R
authors: PR
authors: Harmatz
authors: Mainz University Medical Center, Mainz, Germany.
authors: Eugen
authors: E
authors: Mengel
authors: New Queen Elizabeth Hospital, Birmingham, UK.
authors: Tarekegn
authors: T
authors: Geberhiwot
authors: University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Nicole
authors: N
authors: Muschol
authors: Salford Royal Foundation NHS Trust, Salford, UK.
authors: Christian J
authors: CJ
authors: Hendriksz
authors: Ann & Robert H. Lurie Children's Hospital and Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Barbara K
authors: BK
authors: Burton
authors: Willink Unit, Manchester Centre for Genomic Medicine, Manchester Academic Health Sciences Centre, St Mary's Hospital, University of Manchester, CMFT, Manchester, UK.
authors: Elisabeth
authors: E
authors: Jameson
authors: NY University School of Medicine, New York, New York.
authors: Kenneth I
authors: KI
authors: Berger
authors: Birmingham Children's Hospital, Birmingham, UK.
authors: Andrea
authors: A
authors: Jester
authors: UCSF Benioff Children's Hospital Oakland, Oakland, California.
authors: Marsha
authors: M
authors: Treadwell
authors: BioMarin Europe Ltd., London, UK.
authors: Zlatko
authors: Z
authors: Sisic
authors: BioMarin Pharmaceutical Inc., Novato, California.
authors: Celeste
authors: C
authors: Decker
mesh_terms: D000203:Activities of Daily Living; D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D002648:Child; D002811:Chondroitinsulfatases / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D056947:Enzyme Replacement Therapy; D015444:Exercise; D005260:Female; D006801:Humans; D007632:Keratan Sulfate / Q000652:urine; D008297:Male; D009085:Mucopolysaccharidosis IV / Q000175:diagnosis* / Q000188:drug therapy*; D011788:Quality of Life; D012129:Respiratory Function Tests; D057566:Self Report; D016896:Treatment Outcome; D016138:Walking; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007632:Keratan Sulfate; D002811:Chondroitinsulfatases; C102295:GALNS protein, human
keywords: GALNS protein, human [supplementary concept]; enzyme replacement therapy; mobility limitation; mucopolysaccharidosis IV; physical endurance; safety