Bone Abstracts (2017) 6 OC25 | DOI: 10.1530/boneabs.6.OC25

Biochemical and physical function outcomes after 5 years of treatment with asfotase alfa in adolescents and adults with hypophosphatasia: phase 2 study results

Priya S. Kishnani1, Cheryl Rockman-Greenberg2,3, Andrew E. Denker4, Scott Moseley4 & Michael P. Whyte5

1Duke University Medical Center, Durham, NC, USA; 2Rady Faculty of Health Sciences, Max Rady College of Medicine, The University of Manitoba, Winnipeg, Manitoba, Canada; 3Children’s Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada; 4Alexion Pharmaceuticals, Inc., New Haven, CT, USA; 5Center for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children–St. Louis, St. Louis, MO, USA.

Objective: To evaluate safety and efficacy after 5 years of treatment with asfotase alfa in adolescents and adults with hypophosphatasia (HPP) in a Phase 2, open-label, randomized, dose-ranging study (NCT01163149).

Methods: Treatment with subcutaneous asfotase alfa 0.3 or 0.5 mg/kg per d was compared with no treatment (control) for 6 months in patients aged 13–66 years. After 6 months, all patients (treatment and control groups) received active treatment at 0.5 mg/kg per d; dose was increased after 6–12 months to 1 mg/kg 6x/wk (lowest approved dose). The primary safety outcome was tolerability. Coprimary efficacy outcomes included median change at 6 months in plasma inorganic pyrophosphate (PPi) and pyridoxal-5’-phosphate (PLP) levels. Other measures included 6-Minute Walk Test (6MWT) and Bruininks-Oseretsky Test of Motor Proficiency, 2nd Edition (BOT-2). Data from treatment groups were pooled and reported below as median (min, max).

Results: The study randomized 19 patients (6 aged 13–18 years; 13 aged ≥18 years); 15/19 (79%) completed 5 years of treatment. One patient withdrew due to injection-site hypersensitivity and anaphylactoid reaction (1 episode each). No deaths occurred. The most common treatment-emergent adverse events were injection-site reactions. Decreases in PPi were numerically greater and decreases in PLP were statistically significantly greater at 6 months in treated patients (n=13) vs controls (n=6): PPi, −2.2 μM (−4.4, 0.3) vs −0.2 (−6.8, 1.1; P=0.0715); PLP, −255 ng/ml (−1467, −17) vs 11 (−374, 346; P=0.0285). Decreases were sustained through 5 years (n=16): PPi, −3.0 μM (−5.2, 7.8); PLP, −284 ng/ml (−1580, −25). Distance walked in 6MWT improved from 355 m (10, 620; n=19) before treatment to 450 m (280, 707; n=13) after 5 years of treatment with asfotase alfa, increasing from 76% predicted (42, 101; n=15) to 88% predicted (62, 137; n=11). BOT-2 Running Speed and Agility total point score was 6.5 (0, 39; n=16) before treatment and improved by 4.0 (−5, 18; n=11) after 5y, and BOT-2 Strength total point score was 13.5 (0, 33; n=18) before treatment and improved by 3.5 (−9, 9; n=12) after 5y.

Conclusion: Asfotase alfa was generally well tolerated, numerically decreased circulating PPi and PLP, and improved physical function in adolescents and adults with HPP.

Disclosure: This study was sponsored by Alexion Pharmaceuticals, Inc. PSK is a clinical trial investigator and has received honoraria and travel support from Alexion Pharmaceuticals, Inc., for consulting and participation on advisory boards. AED and SM are employees.

Article tools

My recent searches

No recent searches.