The efficacy and safety of asfotase alfa is being evaluated in adolescents/adults with hypophosphatasia (HPP) in an ongoing Phase 2, open-label, dose-ranging study (NCT01163149). Patients were randomized to receive asfotase alfa 0.3 or 0.5 mg/kg/day or no treatment (control) for 6 months, after which all patients received asfotase alfa 0.5 mg/kg/day, increased 6–12 months later to 1 mg/kg 6 times/week by protocol amendment. This interim post hoc analysis assessed the efficacy and safety of asfotase alfa in adults (≥18 years) with pediatric-onset HPP (n=10). Data from treatment groups were pooled and reported as median (min, max). Changes from baseline to 6 months in inorganic pyrophosphate (PPi) levels (μM) and pyridoxal-5'-phosphate (PLP) levels (ng/mL) (coprimary outcome measures) were greater in treated patients (n=7) vs controls (n=3): PPi, −3.0 (−3.6, 0.3) vs −0.3 (−0.9, 1.1), respectively (P=0.0667); PLP, −255 (−1236, −17) vs 140 (−115, 346), respectively (P=0.0667). Decreases were sustained through 3 years. Distance walked (meters) in the 6-Minute Walk Test (6MWT) increased from 334 (260, 540) at baseline to 417 (319, 578) at 6 months in treated patients (n=7) (change from baseline: 40 [−2, 157] vs −20 [−46, 7] in controls, n=3). Available data at 3 years of treatment (n=8) showed continued improvement (change from baseline: 91 [−45, 200]). Available videos of patients performing the 6MWT showed that 2 patients dependent on ambulatory assistive devices reduced/eliminated their use during treatment with asfotase alfa. Injection-site reactions were the most common treatment-emergent adverse events. No deaths/withdrawals due to adverse events occurred. In adult patients with pediatric-onset HPP, asfotase alfa was well tolerated, decreased PPi and PLP, improved walking ability on the 6MWT (greater than a minimal clinically important difference of 30 meters), and reduced use of ambulatory assistive devices for 2 patients during the 3-year treatment period. Sponsored by Alexion Pharmaceuticals, Inc.