Efficacy and safety of asfotase alfa in infants and young children with hypophosphatasia: a phase 2 open-label study

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Efficacy and safety of asfotase alfa in infants and young children with hypophosphatasia : a phase 2 open-label study. / Hofmann, Christine E; Harmatz, Paul; Vockley, Jerry; Högler, Wolfgang; Nakayama, Hideki; Bishop, Nick; Martos-moreno, Gabriel Á; Moseley, Scott; Fujita, Kenji P; Liese, Johannes; Rockman-greenberg, Cheryl.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 104, No. 7, 01.07.2019, p. 2735-2747.

Research output: Contribution to journalArticle

Harvard

Hofmann, CE, Harmatz, P, Vockley, J, Högler, W, Nakayama, H, Bishop, N, Martos-moreno, GÁ, Moseley, S, Fujita, KP, Liese, J & Rockman-greenberg, C 2019, 'Efficacy and safety of asfotase alfa in infants and young children with hypophosphatasia: a phase 2 open-label study', Journal of Clinical Endocrinology and Metabolism, vol. 104, no. 7, pp. 2735-2747. https://doi.org/10.1210/jc.2018-02335

APA

Hofmann, C. E., Harmatz, P., Vockley, J., Högler, W., Nakayama, H., Bishop, N., Martos-moreno, G. Á., Moseley, S., Fujita, K. P., Liese, J., & Rockman-greenberg, C. (2019). Efficacy and safety of asfotase alfa in infants and young children with hypophosphatasia: a phase 2 open-label study. Journal of Clinical Endocrinology and Metabolism, 104(7), 2735-2747. https://doi.org/10.1210/jc.2018-02335

Vancouver

Author

Hofmann, Christine E ; Harmatz, Paul ; Vockley, Jerry ; Högler, Wolfgang ; Nakayama, Hideki ; Bishop, Nick ; Martos-moreno, Gabriel Á ; Moseley, Scott ; Fujita, Kenji P ; Liese, Johannes ; Rockman-greenberg, Cheryl. / Efficacy and safety of asfotase alfa in infants and young children with hypophosphatasia : a phase 2 open-label study. In: Journal of Clinical Endocrinology and Metabolism. 2019 ; Vol. 104, No. 7. pp. 2735-2747.

Bibtex

@article{602bb5f68e784c1399f49d55d6e0f46e,
title = "Efficacy and safety of asfotase alfa in infants and young children with hypophosphatasia: a phase 2 open-label study",
abstract = "CONTEXT: Long-term data on enzyme replacement treatment of hypophosphatasia (HPP) are limited.OBJECTIVE: To evaluate efficacy and safety of asfotase alfa in patients aged ≤5 years with HPP followed for up to 6 years.DESIGN: Phase 2 open-label study (July 2010 to September 2016).SETTING: Twenty-two sites; 12 countries.PARTICIPANTS: Sixty-nine patients [median (range) age: 16.0 (0.02 to 72) months] with severe HPP and sign/symptom onset before age 6 months.INTERVENTION: Asfotase alfa 2 mg/kg three times/week or 1 mg/kg six times/week subcutaneously.MAIN OUTCOME MEASURES: Primary efficacy measure: Radiographic Global Impression of Change (RGI-C) score [-3 (severe worsening) to +3 (complete/near-complete healing)]. Additional outcome measures: respiratory status, growth, and safety. Post hoc analysis: characteristics of radiographic responders vs nonresponders at Year 1 (RGI-C: ≥+2 vs <+2).RESULTS: During median (minimum, maximum) 2.3 (0.02, 5.8) years of treatment, RGI-C scores improved significantly at Month 6 [+2.0 (-1.7, +3.0)], Year 1 [+2.0 (-2.3, +3.0)], and Last Assessment [+2.3 (-2.7, +3.0); P < 0.0001 all]. Of 24 patients requiring respiratory support at Baseline, 11 (46%) no longer needed support. Height/weight z scores generally increased. Nine patients died (13%). All patients experienced at least one adverse event; pyrexia was most common. Compared with responders [n = 50 (72%)], nonresponders [n = 19 (28%)] had more severe disease at Baseline and a higher rate of neutralizing antibodies (NAbs) at Last Assessment.CONCLUSIONS: Most infants/young children given asfotase alfa showed early radiographic and clinical improvement sustained up to 6 years; radiographic nonresponders had more severe disease and more frequent NAbs at Last Assessment.",
author = "Hofmann, {Christine E} and Paul Harmatz and Jerry Vockley and Wolfgang H{\"o}gler and Hideki Nakayama and Nick Bishop and Martos-moreno, {Gabriel {\'A}} and Scott Moseley and Fujita, {Kenji P} and Johannes Liese and Cheryl Rockman-greenberg",
note = "Copyright {\textcopyright} 2019 Endocrine Society.",
year = "2019",
month = jul
day = "1",
doi = "10.1210/jc.2018-02335",
language = "English",
volume = "104",
pages = "2735--2747",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Endocrine Society",
number = "7",

}

RIS

TY - JOUR

T1 - Efficacy and safety of asfotase alfa in infants and young children with hypophosphatasia

T2 - a phase 2 open-label study

AU - Hofmann, Christine E

AU - Harmatz, Paul

AU - Vockley, Jerry

AU - Högler, Wolfgang

AU - Nakayama, Hideki

AU - Bishop, Nick

AU - Martos-moreno, Gabriel Á

AU - Moseley, Scott

AU - Fujita, Kenji P

AU - Liese, Johannes

AU - Rockman-greenberg, Cheryl

N1 - Copyright © 2019 Endocrine Society.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - CONTEXT: Long-term data on enzyme replacement treatment of hypophosphatasia (HPP) are limited.OBJECTIVE: To evaluate efficacy and safety of asfotase alfa in patients aged ≤5 years with HPP followed for up to 6 years.DESIGN: Phase 2 open-label study (July 2010 to September 2016).SETTING: Twenty-two sites; 12 countries.PARTICIPANTS: Sixty-nine patients [median (range) age: 16.0 (0.02 to 72) months] with severe HPP and sign/symptom onset before age 6 months.INTERVENTION: Asfotase alfa 2 mg/kg three times/week or 1 mg/kg six times/week subcutaneously.MAIN OUTCOME MEASURES: Primary efficacy measure: Radiographic Global Impression of Change (RGI-C) score [-3 (severe worsening) to +3 (complete/near-complete healing)]. Additional outcome measures: respiratory status, growth, and safety. Post hoc analysis: characteristics of radiographic responders vs nonresponders at Year 1 (RGI-C: ≥+2 vs <+2).RESULTS: During median (minimum, maximum) 2.3 (0.02, 5.8) years of treatment, RGI-C scores improved significantly at Month 6 [+2.0 (-1.7, +3.0)], Year 1 [+2.0 (-2.3, +3.0)], and Last Assessment [+2.3 (-2.7, +3.0); P < 0.0001 all]. Of 24 patients requiring respiratory support at Baseline, 11 (46%) no longer needed support. Height/weight z scores generally increased. Nine patients died (13%). All patients experienced at least one adverse event; pyrexia was most common. Compared with responders [n = 50 (72%)], nonresponders [n = 19 (28%)] had more severe disease at Baseline and a higher rate of neutralizing antibodies (NAbs) at Last Assessment.CONCLUSIONS: Most infants/young children given asfotase alfa showed early radiographic and clinical improvement sustained up to 6 years; radiographic nonresponders had more severe disease and more frequent NAbs at Last Assessment.

AB - CONTEXT: Long-term data on enzyme replacement treatment of hypophosphatasia (HPP) are limited.OBJECTIVE: To evaluate efficacy and safety of asfotase alfa in patients aged ≤5 years with HPP followed for up to 6 years.DESIGN: Phase 2 open-label study (July 2010 to September 2016).SETTING: Twenty-two sites; 12 countries.PARTICIPANTS: Sixty-nine patients [median (range) age: 16.0 (0.02 to 72) months] with severe HPP and sign/symptom onset before age 6 months.INTERVENTION: Asfotase alfa 2 mg/kg three times/week or 1 mg/kg six times/week subcutaneously.MAIN OUTCOME MEASURES: Primary efficacy measure: Radiographic Global Impression of Change (RGI-C) score [-3 (severe worsening) to +3 (complete/near-complete healing)]. Additional outcome measures: respiratory status, growth, and safety. Post hoc analysis: characteristics of radiographic responders vs nonresponders at Year 1 (RGI-C: ≥+2 vs <+2).RESULTS: During median (minimum, maximum) 2.3 (0.02, 5.8) years of treatment, RGI-C scores improved significantly at Month 6 [+2.0 (-1.7, +3.0)], Year 1 [+2.0 (-2.3, +3.0)], and Last Assessment [+2.3 (-2.7, +3.0); P < 0.0001 all]. Of 24 patients requiring respiratory support at Baseline, 11 (46%) no longer needed support. Height/weight z scores generally increased. Nine patients died (13%). All patients experienced at least one adverse event; pyrexia was most common. Compared with responders [n = 50 (72%)], nonresponders [n = 19 (28%)] had more severe disease at Baseline and a higher rate of neutralizing antibodies (NAbs) at Last Assessment.CONCLUSIONS: Most infants/young children given asfotase alfa showed early radiographic and clinical improvement sustained up to 6 years; radiographic nonresponders had more severe disease and more frequent NAbs at Last Assessment.

UR - http://www.scopus.com/inward/record.url?scp=85064233580&partnerID=8YFLogxK

U2 - 10.1210/jc.2018-02335

DO - 10.1210/jc.2018-02335

M3 - Article

C2 - 30811537

VL - 104

SP - 2735

EP - 2747

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 7

ER -