Asfotase alfa mineralizes the HPP skeleton, including the ribs, and improves respiratory function and survival in life-threatening perinatal and infantile HPP.

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Background: Our Phase 2, open-label study of 11 infants and young children with lifethreatening perinatal or infantile hypophosphatasia (HPP) demonstrated 1-year safety and efficacy of asfotase alfa, an enzyme replacement therapy. We report outcomes over ~7 years. Methods: Patients received asfotase alfa (1 mg/kg thrice weekly subcutaneously; adjusted to 3 mg/kg thrice weekly if required). HPP skeletal manifestations were evaluated on the Radiographic Global Impression of Change (RGI-C) scale (−3=severe worsening; +3=complete/near complete healing). Respiratory support, growth, and cognitive and motor function were also evaluated. Findings: Ten patients completed a 6-month treatment period and entered an extension; nine received asfotase alfa for ≥6 years and completed the study, with four treated >7 years. Skeletal healing was sustained over 7 years of treatment; all evaluable patients had RGI-C scores ≥+2 at Years 6 and 7. No patient who completed the study required respiratory support after Year 4. Weight Z-scores improved to within normal range from Year 3 to study end; length/height Z-scores improved but remained below normal. Age-equivalent scores on Gross Motor, Fine Motor, and Cognitive subscales of the Bayley Scales of Infant and Toddler Development also improved. Treatment was generally well tolerated; adverse events were similar to those previously published. Interpretation: Patients with perinatal or infantile HPP treated with asfotase alfa for up to 7 years showed early, sustained improvements in skeletal mineralization. Respiratory function, growth, and cognitive and motor function also improved. Asfotase alfa is safe and effective in perinatal/infantile HPP.

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