Abstract | BACKGROUND: METHODS: FINDINGS: All patients developed ADA against PAL, peaking by 6 months and then stabilizing. Most developed transient antibody responses against PEG, peaking by 3 months, then returning to baseline by 9 months. Binding of ADA to pegvaliase led to CIC formation and complement activation, which were highest during early treatment. Blood Phe decreased over time as CIC levels and complement activation declined and pegvaliase dosage increased. HAEs were most frequent during early treatment and declined over time. No patient with acute systemic hypersensitivity events tested positive for pegvaliase-specific IgE near the time of the event. Laboratory evidence was consistent with immune complex-mediated type III hypersensitivity. No evidence of pegvaliase-associated IC-mediated end organ damage was noted. INTERPRETATION: Despite a universal ADA response post- pegvaliase administration, adult patients with PKU achieved substantial and sustained blood Phe reductions with a manageable safety profile. FUND: BioMarin Pharmaceutical Inc.
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Authors | Soumi Gupta, Kelly Lau, Cary O Harding, Gillian Shepherd, Ryan Boyer, John P Atkinson, Vijaya Knight, Joy Olbertz, Kevin Larimore, Zhonghu Gu, Mingjin Li, Orli Rosen, Stephen J Zoog, Haoling H Weng, Becky Schweighardt |
Journal | EBioMedicine
(EBioMedicine)
Vol. 37
Pg. 366-373
(Nov 2018)
ISSN: 2352-3964 [Electronic] Netherlands |
PMID | 30366815
(Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)
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Copyright | Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Antibodies
- Antigen-Antibody Complex
- Complement C3
- Complement C4
- Recombinant Proteins
- Phenylalanine
- Phenylalanine Ammonia-Lyase
- pegvaliase
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Topics |
- Adult
- Antibodies
(blood, immunology)
- Antigen-Antibody Complex
(blood, immunology)
- Complement C3
(immunology, metabolism)
- Complement C4
(immunology, metabolism)
- Drug Hypersensitivity
(blood, immunology)
- Female
- Humans
- Male
- Phenylalanine
(blood, immunology)
- Phenylalanine Ammonia-Lyase
(administration & dosage, adverse effects)
- Phenylketonurias
(blood, drug therapy, immunology)
- Recombinant Proteins
(administration & dosage, adverse effects)
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