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

Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia.

Author information

1
Shriners Hospital for Children (M.P.W.) and Division of Bone and Mineral Diseases at Washington University School of Medicine (M.P.W.), St Louis, Missouri 63110; University of Manitoba and Children's Hospital Research Institute of Manitoba (C.R.-G.), Winnipeg, MB R3T 2N2 Canada; Graduate School of Medicine (K.O.), Osaka University, Osaka, 565-0871 Japan; Alexion Pharmaceuticals, Inc. (R.R., S.M., A.M., D.D.T.), Cheshire, Connecticut 06410; Department of Human Metabolism (N.B.), University of Sheffield, Sheffield, S10 2TN United Kingdom; Sheffield Children's Hospital (N.B.), Sheffield, S10 2TH United Kingdom; University Children's Hospital (C.H.), University of Würzburg, Würzburg, D-97080 Germany.

Abstract

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:

ClinicalTrials.gov NCT00744042 NCT01176266 NCT01205152 NCT01419028.

PMID:
26529632
PMCID:
PMC4701846
DOI:
10.1210/jc.2015-3462
[Indexed for MEDLINE]
Free PMC Article

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