Searchable abstracts of presentations at key conferences on calcified tissues
Bone Abstracts (2019) 7 P76 | DOI: 10.1530/boneabs.7.P76

ICCBH2019 Poster Presentations (1) (226 abstracts)

Safety profile of asfotase alfa treatment of patients with hypophosphatasia: a pooled analysis

Michael P Whyte 1 , Nick Bishop 2 , Jawad Hasan 3 , Christine Hofmann 4 , Wolfgang Högler 5 , Cheryl Rockman-Greenberg 6 , Veruska Sena 3 , Shanggen Zhou 7 & Priya S Kishnani 8

1Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, Saint Louis, USA; 2Department of Oncology and Metabolism, University of Sheffield and Sheffield Children’s NHS FT, Sheffield, UK; 3Alexion Pharmaceuticals, Inc., Boston, USA; 4University Children’s Hospital, University of Würzburg, Würzburg, Germany; 5Department of Pediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria; 6University of Manitoba, Rady Faculty of Health Sciences, Max Rady College of Medicine, and Children’s Hospital Research Institute of Manitoba, Winnipeg, Canada; 7Covance, Inc., Princeton, USA; 8Department of Pediatrics, Duke University Medical Center, Durham, USA.

Objectives: Asfotase alfa (AA), an enzyme replacement therapy, is the only approved treatment for pediatric-onset hypophosphatasia (HPP). We evaluated the safety profile of AA from the clinical trial program spanning pediatric and adult patients.

Methods: Safety data were pooled from 4 open-label, multicenter studies in children aged ≤3 years (study 002/003 [NCT00744042/NCT01205152]; n=11) and ≤5 years (study 010-10 [NCT01176266]; n=69) with HPP presenting before age 6 months; children aged 5–12 years with HPP (study 006/008 [NCT00952484/NCT01203826]; n=13); and adolescents/adults aged 13–65 years with HPP presenting at any age (study 009 [NCT01163149]; n=19). Safety events after the studies ended were not included.

Results: Overall, 112 patients (median [min, max] age at enrollment: 3.2 [0, 66.5] y; female: 51%) had a median (min, max) treatment duration of 2.7 years (1 d, 7.5 y) and average weekly total dose of 5.95 (2.1, 11.9) mg/kg. Adverse events (AEs) occurred in all patients; 26% of events were considered treatment-related; 74% were mild, and 21% were moderate. ISRs were the most common treatment-related AEs (73%). Ten (9%) patients experienced serious treatment-related AEs. Serious AEs of special interest were craniosynostosis (25%), injection-associated reactions (5%), injection site reactions (ISRs; 2%), ectopic calcifications (2%), and liver abnormalities/disease (2%). Ten infants with severe HPP (aged 1 d–20 mo at enrollment) died, four of pneumonia/sepsis and 1 each of respiratory failure and cerebral death, HPP-related complications, severe respiratory failure, cardiopulmonary arrest, severe cardiopulmonary insufficiency, and transtentorial and cerebellar tonsillar herniation from cerebral edema. Most deaths were considered related to underlying HPP. One death, attributed to pneumonia, was reported as possibly related to AA. AEs leading to withdrawal occurred in 11 (10%) patients; pneumonia and respiratory failure were reported in ≥2 patients. During treatment, 97/109 (89%) patients tested positive for anti-AA immunoglobulin G (IgG) antibodies, and 55 (57%) of these showed presence of neutralizing antibodies (NAbs). No relationship between patient anti-AA IgG/NAb status and treatment-emergent AEs was observed.

Conclusions: In this pooled analysis of mostly prepubescent children (84%) receiving AA for up to 7 years, ISRs were the most common treatment-related AEs.

Disclosure: MPW, NB, CH, WH, CRG, and PSK are clinical study investigators and have received honoraria, and/or institutional grant funding/research support, and/or speaker/consulting fees, and/or travel support from Alexion Pharmaceuticals, Inc. JH and VS are employees of, and may own stock/options, in Alexion Pharmaceuticals, Inc., which sponsored the study. SZ is an employee of Covance, Inc., and provided statistical services for this analysis under contract to Alexion Pharmaceuticals, Inc.

Volume 7

9th International Conference on Children's Bone Health


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