Background/objectives: Hypophosphatasia (HPP) results from inactivating mutation (s) in the gene for tissue non-specific alkaline phosphatase (TNSALP). Long-term efficacy and tolerability of asfotase alfa, a recombinant human TNSALP, was evaluated in patients with lifethreatening perinatal and infantile HPP. Materials/methods: Radiographic Global Impression of Change scale (RGI-C, -3 to +3), Rickets Severity Scale (RSS; 0 to 10) and respiratory status were assessed during asfotase alfa treatment (Rx; SC injection, 3x/ wk, 1-3 mg/kg) for >3 yrs. Results: Eleven patients (median age 6.8 months) were enrolled; one subsequently withdrew and one died (unrelated to treatment). Median treatment duration was 35months. Asfotase alfa waswell tolerated. Three SAEs were reported as possibly treatment-related; craniosynostosis (a known complication of HPP), conductive deafness and chronic hepatitis. Median RGI-C (+2.50, p=0.008) and median change in RSS (-6.25, p= 0.016) showed sustained improvement from baseline at 3 years (n=8). Ten patients required respiratory support at some time during the first 48 weeks, after which three remained on support. Two subsequently discontinued support and one improved to supplemental oxygen. Probability of survival at 3 years was 90 %. Conclusion: Infants and young children with life-threatening HPP treated with asfotase alfa show sustained improvement in skeletal mineralization and respiratory status for >3 years.
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