Details

Autor(en) / Beteiligte

• Hofmann, Christine E
• Harmatz, Paul
• Vockley, Jerry
• Högler, Wolfgang
• Nakayama, Hideki
• Bishop, Nick
• Martos-Moreno, Gabriel Á
• Moseley, Scott
• Fujita, Kenji P
• Liese, Johannes
• Rockman-Greenberg, Cheryl

Titel

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

Link zum Volltext

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.