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Efficacy and Safety of Asfotase Alfa in Infants and Young Children With Hypophosphatasia: A Phase 2 Open-Label Study
Ist Teil von
The journal of clinical endocrinology and metabolism, 2019-07, Vol.104 (7), p.2735-2747
Ort / Verlag
Washington, DC: Endocrine Society
Erscheinungsjahr
2019
Quelle
Oxford Journals 2020 Medicine
Beschreibungen/Notizen
Abstract
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.
Most infants and young children with hypophosphatasia, treated with asfotase alfa, showed improved skeletal manifestations, respiratory function, and growth within 1 year, maintained up to 6 years.