title: Safety and efficacy of treatment with asfotase alfa in patients with hypophosphatasia: Results from a Japanese clinical trial.
abstract: OBJECTIVE
  Hypophosphatasia (HPP) is a rare skeletal disease characterized by hypomineralization and low alkaline phosphatase activity. Asfotase alfa (AA) has been recently developed to treat HPP complications. This study evaluated its safety and efficacy in Japan.
  
  
  METHODS
  Open-label, multicentre, prospective trial. Patients were enrolled in 11 hospitals from June 2014 to July 2015.
  
  
  METHODS
  Thirteen patients (9 females, 4 males) ages 0 days to 34 years at baseline were enrolled and treated with AA (2 mg/kg three times weekly subcutaneously in all but one patient). All had ALPL gene mutations. HPP forms were perinatal (n=6), infantile (n=5), childhood (n=1) and adult (n=1).
  
  
  METHODS
  Safety determined from adverse events (AEs) and laboratory data was the primary outcome measure. Efficacy was assessed as a secondary outcome measure from overall survival, respiratory status, rickets severity and gross motor development.
  
  
  RESULTS
  Injection site reactions were the most frequent AEs. Serious AEs possibly related to treatment were convulsion and hypocalcaemia observed in a patient with the perinatal form. In addition, hypercalcaemia and/or hyperphosphatemia was observed in three patients with the infantile form and a low-calcium and/or low-phosphate formula was given to these patients. With respect to efficacy, all patients survived and the radiographic findings, developmental milestones and respiratory function improved.
  
  
  CONCLUSIONS
  Asfotase alfa therapy improved skeletal, respiratory and physical symptoms with a few serious AEs in patients with HPP. Our results add support to the safety and efficacy of AA therapy for HPP patients.
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Taichi
authors.identifier: http://orcid.org/0000-0002-3531-884X
authors.initials: T
authors.lastname: Kitaoka
authors.affiliation: Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tajima
authors.affiliation: Division of Pediatrics, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nagasaki
authors.affiliation: Division of Pediatrics, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Department of Pediatric Nephrology and Metabolism, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Katsusuke
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Toshimi
authors.initials: T
authors.lastname: Michigami
authors.affiliation: Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okada
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Miyagi, Japan.
authors.forename: Ikuma
authors.initials: I
authors.lastname: Fujiwara
authors.affiliation: Department of Pediatrics, Showa General Hospital, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kokaji
authors.affiliation: Division of Endocrinology and Metabolism, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mochizuki
authors.affiliation: Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.affiliation: Department of Pediatrics, Nagara Medical Center, Gifu, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tatebayashi
authors.affiliation: Division of Clinical Genetics, Nippon Medical School Hospital, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yatsuga
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Takuo
authors.initials: T
authors.lastname: Kubota
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ozono
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics* / Q000627:therapeutic use; D002118:Calcium / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D054559:Hyperphosphatemia / Q000139:chemically induced; D007014:Hypophosphatasia / Q000188:drug therapy*; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D009154:Mutation; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; C548267:ALPL protein, human; D000469:Alkaline Phosphatase; D002118:Calcium; C570710:asfotase alfa
keywords: alkaline phosphatase; asfotase alfa; convulsion; enzyme replacement therapy; hypocalcaemia; hypophosphatasia