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Bone Abstracts (2017) 6 OC23 | DOI: 10.1530/boneabs.6.OC23

ICCBH2017 Oral Communications (1) (26 abstracts)

Sustained radiographic and functional improvements with asfotase alfa treatment from up to 7 years in children with hypophosphatasia

Michael P. Whyte 1 , Cheryl Rockman-Greenberg 2, , Scott Moseley 4 , Andrew E. Denker 4 & William H. McAlister 5

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

Objective: Children with hypophosphatasia (HPP) treated with asfotase alfa in a Phase 2 study (NCT00952484) and its open-label extension (NCT01203826) experienced significant improvements in skeletal mineralization and physical function that were sustained through 5 years of treatment (1). Herein, we report data from these studies with a maximum of 7 years of treatment.

Methods: Children with HPP aged 6–12 years at baseline received asfotase alfa (3 mg/kg per wk subcutaneously, later increased to 6 mg/kg per wk). Radiographs of the hand/wrist and knees were assessed using the Radiographic Global Impression of Change (RGI-C) scale and Rickets Severity Scale (RSS). Additional outcomes included growth, functional ability/disability (6-Minute Walk Test (6MWT); Bruininks-Oseretsky Test of Motor Proficiency, 2nd Edition (BOT-2), Strength and Agility Composite Standard Score; Child Health Assessment Questionnaire Disability Index (CHAQ-DI)), and safety.

Results: All 12 children who entered the extension phase received asfotase alfa for 7 years. Final RGI-C and RSS scores measured improved HPP-related skeletal manifestations that were sustained through end of study (Table 1). Improved growth (height/weight Z-scores) and function (6MWT, BOT-2 Strength and Agility, CHAQ-DI) were also sustained through end of study (Table 1). Mild-to-moderate injection site reactions were reported in all patients (e.g., erythema, macule, lipohypertrophy); 1 event of injection site atrophy was assessed as severe. No serious adverse events, including deaths, were reported.

Table 1
Median (min, max)
OutcomeReference range for healthy peersBaseline (n=13)aLast observation (n=12)aP value
RGI-CNAb2.8 (2.0, 3.0)0.0005c
RSS0=no rickets3.0 (0.5, 6.0)0 (0, 1.0)ND
Height Z-score−2 to +2−1.26 (−6.6, 0)−0.69 (−5.4, 0.4)0.0007d
Weight Z-score−2 to +2−1.21 (−8.2, 2.3)−0.15 (−5.4, 2.7)0.0004d
6MWT, % predicted80% to 120%61% (29%, 82%)85% (69%, 104%)e0.0006f
BOT-2, Strength and Agility Composite Standard Score40 to 6028 (20, 37)51 (34, 62)e<0.0001f
CHAQ-DIg0=no disability1 (0, 2.25)0 (0,0.5)0.0004f
aOne patient withdrew after 1 month for elective surgery. bBaseline value not applicable (NA) because RGI-C describes change from baseline; RGI-C range: −3 (severe worsening) to +3 (complete/near complete healing). cWilcoxon signed-rank test assessing if median is 0. dWilcoxon signed-rank test assessing if median change from baseline is 0. en=11 for last observation for 6MWT and BOT-2. ft-test assessing if mean change from baseline is 0. gCHAQ-DI range: 0 to 3, with higher scores indicating greater disability. ND=not determined.

Conclusion: Improvements in HPP-related skeletal manifestations, growth, and functional ability with asfotase alfa treatment in children with HPP were sustained for up to 7 years. Treatment was generally well tolerated.

Disclosure: This study was sponsored by Alexion Pharmaceuticals, Inc. MPW and WHM are clinical trial investigators and have received honoraria, travel support, and research grant support from Alexion Pharmaceuticals, Inc. CRG is a clinical trial investigator and has received honoraria, travel support, and research grant support from Alexion Pharmaceuticals, Inc., for consulting and participating on advisory boards. SM and AED are employees of and may own stock/options in Alexion Pharmaceuticals, Inc., which sponsored the study.

1. Whyte et al. JCI Insight. 2016;1:e85971.

Volume 6

8th International Conference on Children's Bone Health


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