Asfotase alfa treatment improves survival for perinatal and infantile hypophosphatasia
MP Whyte, C Rockman-Greenberg… - The Journal of …, 2016 - academic.oup.com
MP Whyte, C Rockman-Greenberg, K Ozono, R Riese, S Moseley, A Melian, DD Thompson…
The Journal of Clinical Endocrinology, 2016•academic.oup.comContext: 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 …
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 …
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.
Oxford University Press