Efficacy and safety of asfotase alfa in infants and young children with hypophosphatasia: a phase 2 open-label study

Research output: Contribution to journalArticle


  • Christine E Hofmann
  • Paul Harmatz
  • Jerry Vockley
  • Wolfgang Högler
  • Hideki Nakayama
  • And 6 others
  • Nick Bishop
  • Gabriel Á Martos-moreno
  • Scott Moseley
  • Kenji P Fujita
  • Johannes Liese
  • Cheryl Rockman-greenberg

Colleges, School and Institutes

External organisations

  • University Children’s Hospital, University of Würzburg, Würzburg, Germany
  • UCSF Benioff Children’s Hospital Oakland, Oakland, CA, USA
  • University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, PA, USA
  • Department of Paediatrics and Adolescent Medicine, Johannes Kepler University, Linz, Austria
  • Fukuoka Higashi Medical Center, Fukuoka, Japan
  • Sheffield Children’s Hospital and University of Sheffield, Sheffield, UK
  • Hospital Infantil Universitario Niño Jesús, Universidad Autónoma de Madrid, CIBERobn, ISCIII, Madrid, Spain
  • Alexion Pharmaceuticals, Inc., Boston, MA, USA
  • Children’s Hospital Research Institute of Manitoba and University of Manitoba, Winnipeg, Manitoba, Canada


CONTEXT: Long-term data on enzyme replacement treatment of hypophosphatasia (HPP) are limited.

OBJECTIVE: To evaluate efficacy and safety of asfotase alfa in patients aged ≤5 years with HPP followed for up to 6 years.

DESIGN: Phase 2 open-label study (July 2010 to September 2016).

SETTING: Twenty-two sites; 12 countries.

PARTICIPANTS: Sixty-nine patients [median (range) age: 16.0 (0.02 to 72) months] with severe HPP and sign/symptom onset before age 6 months.

INTERVENTION: Asfotase alfa 2 mg/kg three times/week or 1 mg/kg six times/week subcutaneously.

MAIN OUTCOME MEASURES: Primary efficacy measure: Radiographic Global Impression of Change (RGI-C) score [-3 (severe worsening) to +3 (complete/near-complete healing)]. Additional outcome measures: respiratory status, growth, and safety. Post hoc analysis: characteristics of radiographic responders vs nonresponders at Year 1 (RGI-C: ≥+2 vs <+2).

RESULTS: During median (minimum, maximum) 2.3 (0.02, 5.8) years of treatment, RGI-C scores improved significantly at Month 6 [+2.0 (-1.7, +3.0)], Year 1 [+2.0 (-2.3, +3.0)], and Last Assessment [+2.3 (-2.7, +3.0); P < 0.0001 all]. Of 24 patients requiring respiratory support at Baseline, 11 (46%) no longer needed support. Height/weight z scores generally increased. Nine patients died (13%). All patients experienced at least one adverse event; pyrexia was most common. Compared with responders [n = 50 (72%)], nonresponders [n = 19 (28%)] had more severe disease at Baseline and a higher rate of neutralizing antibodies (NAbs) at Last Assessment.

CONCLUSIONS: Most infants/young children given asfotase alfa showed early radiographic and clinical improvement sustained up to 6 years; radiographic nonresponders had more severe disease and more frequent NAbs at Last Assessment.

Bibliographic note

Copyright © 2019 Endocrine Society.


Original languageEnglish
Pages (from-to)2735-2747
Number of pages13
JournalJournal of Clinical Endocrinology and Metabolism
Issue number7
Early online date27 Feb 2019
Publication statusPublished - 1 Jul 2019