title: Safety and efficacy of enzyme replacement therapy with idursulfase beta in children aged younger than 6 years with Hunter syndrome.
abstract: Idursulfase beta (Hunterase®) has been used for enzyme replacement therapy (ERT) of patients with mucopolysaccharidosis II (MPS II, Hunter syndrome) aged 6 years or older since 2012 in Korea. The objective of this study was to evaluate the safety and efficacy of ERT with idursulfase beta in Hunter syndrome children younger than 6 years. This study was a 52-week, single center, single arm, open-label clinical trial (NCT01645189). Idursulfase beta (0.5mg/kg/week) was administered intravenously for 52 weeks. The primary endpoint was safety assessed by adverse events (AEs). Secondary endpoints included vital signs, physical examination, ECG, laboratory tests, anti-idursulfase antibodies, and efficacy represented by changes in urinary glycosaminoglycan (GAG) at week 53 from baseline. In addition, growth indices and developmental milestones (Denver II test) were evaluated as exploratory variables. All six patients experienced at least one AE. A total of 109 AEs were reported. One patient experienced a serious AE (hospitalization due to gastroenteritis) that was considered not to be treatment related. One patient (16.7%) experienced infusion-related adverse drug reactions (ADRs), developing urticaria six times and a cough five times. There were no serious ADRs and no clinically significant changes in vital signs, physical exam, laboratory parameters, or ECG. Of the six patients, four (66.7%) showed anti-idursulfase antibodies and neutralizing antibodies on at least one occasion during the study. At week 53, urinary GAG was significantly reduced by -35.1±30.6mgGAG/g creatine from baseline (P=0.038). This study indicates that the safety and efficacy of idursulfase beta are similar to those reported in Hunter syndrome patients aged 6 years or older.
authors.affiliation: Department of Medical Genetics, Ajou University Hospital, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Sohn
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Sung Yoon
authors.initials: SY
authors.lastname: Cho
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Yonghee
authors.initials: Y
authors.lastname: Kwun
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Rimm
authors.initials: R
authors.lastname: Huh
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: jindk@skku.edu.
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Jin
mesh_terms: D061605:Administration, Intravenous / Q000009:adverse effects; D000906:Antibodies / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D002648:Child; D002675:Child, Preschool; D056947:Enzyme Replacement Therapy; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D007066:Iduronate Sulfatase / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D016532:Mucopolysaccharidosis II / Q000188:drug therapy*; D056910:Republic of Korea; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D057134:Antibodies, Neutralizing; D006025:Glycosaminoglycans; D007066:Iduronate Sulfatase; C517982:idursulfase
keywords: Children; Enzyme replacement therapy; Hunter syndrome; Idursulfase beta; Mucopolysaccharidosis II