Poster Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Biochemical and physical function outcomes in adults with pediatric-onset hypophosphatasia treated with asfotase alfa for up to 3 years: interim results from a Phase 2 study (#422)

Priya Kishnani 1 , Marisa Gayron 2 , Andrew E. Denker 2 , Eric Watsky 2 , Cheryl R. Rockman-Greenberg 3
  1. Duke University Medical Center, Durham, NC, USA
  2. Alexion Pharmaceuticals, Inc., New Haven, CT, USA
  3. University of Manitoba, Winnipeg, Manitoba, Canada

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.