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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.

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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.



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.


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.


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.


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


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


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


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.


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.

[Indexed for MEDLINE]
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