Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia

J Clin Endocrinol Metab. 2016 Jan;101(1):334-42. doi: 10.1210/jc.2015-3462. Epub 2015 Nov 3.


Context: Hypophosphatasia (HPP) is an inborn error of metabolism that, in its most severe perinatal and infantile forms, results in 50-100% mortality, typically from respiratory complications.

Objectives: Our objective was to better understand the effect of treatment with asfotase alfa, a first-in-class enzyme replacement therapy, on mortality in neonates and infants with severe HPP.

Design/setting: Data from patients with the perinatal and infantile forms of HPP in two ongoing, multicenter, multinational, open-label, phase 2 interventional studies of asfotase alfa treatment were compared with data from similar patients from a retrospective natural history study.

Patients: Thirty-seven treated patients (median treatment duration, 2.7 years) and 48 historical controls of similar chronological age and HPP characteristics.

Interventions: Treated patients received asfotase alfa as sc injections either 1 mg/kg six times per week or 2 mg/kg thrice weekly.

Main outcome measures: Survival, skeletal health quantified radiographically on treatment, and ventilatory status were the main outcome measures for this study.

Results: Asfotase alfa was associated with improved survival in treated patients vs historical controls: 95% vs 42% at age 1 year and 84% vs 27% at age 5 years, respectively (P < .0001, Kaplan-Meier log-rank test). Whereas 5% (1/20) of the historical controls who required ventilatory assistance survived, 76% (16/21) of the ventilated and treated patients survived, among whom 75% (12/16) were weaned from ventilatory support. This better respiratory outcome accompanied radiographic improvements in skeletal mineralization and health.

Conclusions: Asfotase alfa mineralizes the HPP skeleton, including the ribs, and improves respiratory function and survival in life-threatening perinatal and infantile HPP.

Trial registration: NCT00744042 NCT01176266 NCT01205152 NCT01419028.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Alkaline Phosphatase / administration & dosage
  • Alkaline Phosphatase / therapeutic use*
  • Bone Density
  • Child, Preschool
  • Enzyme Replacement Therapy
  • Female
  • Humans
  • Hypophosphatasia / drug therapy*
  • Hypophosphatasia / mortality
  • Hypophosphatasia / therapy
  • Immunoglobulin G / administration & dosage
  • Immunoglobulin G / therapeutic use*
  • Infant
  • Infant, Newborn
  • Injections, Subcutaneous
  • Kaplan-Meier Estimate
  • Male
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / therapeutic use*
  • Respiration, Artificial
  • Respiratory Function Tests
  • Survival Analysis
  • Treatment Outcome


  • Immunoglobulin G
  • Recombinant Fusion Proteins
  • Alkaline Phosphatase
  • asfotase alfa

Associated data