Trial reportEBioMedicine2018
Association of immune response with efficacy and safety outcomes in adults with phenylketonuria administered pegvaliase in phase 3 clinical trials.
Trial report in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Italian national consensus statement on management and pharmacological treatment of phenylketonuria.Orphanet journal of rare diseases · 2021Pooled it
- Pharmacokinetic, pharmacodynamic, and immunogenic rationale for optimal dosing of pegvaliase, a PEGylated bacterial enzyme, in adult patients with phenylketonuria.Clinical and translational science · 2021Trial
- Long-term comparative effectiveness of pegvaliase versus standard of care comparators in adults with phenylketonuria.Molecular genetics and metabolismTrial
- Clinical experience with Pegvaliase in phenylketonuria: A retrospective chart review of outcomes, safety, and dosing patterns.Molecular genetics and metabolism reports · 2026Article
- Long-Term Safety and Efficacy of Pegvaliase in Japanese Adults With Phenylketonuria: Final Results of a Phase III Trial.JIMD reports · 2026Article
- PEGylated Proteins: How Much Does Molecular Weight Matter?Clinical pharmacokinetics · 2025Review
- Nanoencapsulation platform for oral delivery of peptides: In vitro stabilization of AvPAL and formulation of a gastrointestinal-resistant luciferase.Materials today. Bio · 2025Article
- Lessons learned from 5 years of pegvaliase in US clinics: A case series.Molecular genetics and metabolism reports · 2025Article
- Pegvaliase-induced immediate hypersensitivity reaction after the discontinuation of antihistamine therapy in a patient with phenylketonuria - Case report.Molecular genetics and metabolism reports · 2024Article
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- First successful outcomes of pegvaliase (PALYNZIQ) in children.BMC medical genomics · 2024Article
- Development of anti-PEG IgG/IgM/IgE ELISA assays for profiling anti-PEG immunoglobulin response in PEG-sensitized individuals and patients with alpha-gal allergy.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Optimizing Pharmacological and Immunological Properties of Therapeutic Proteins Through PEGylation: Investigating Key Parameters and Their Impact.Drug design, development and therapy · 2024Review
- Nutritional status of adults with phenylketonuria on pegvaliase: A 15-month prospective study.Molecular genetics and metabolism reports · 2023Article
- Natural Protein Intake in Children with Phenylketonuria: Prescription vs. Actual Intakes.Nutrients · 2023Article
- Antibodies against Poly(ethylene glycol) Activate Innate Immune Cells and Induce Hypersensitivity Reactions to PEGylated Nanomedicines.ACS nano · 2023Article
- Real-world treatment, dosing, and discontinuation patterns among patients treated with pegvaliase for phenylketonuria: Evidence from dispensing data.Molecular genetics and metabolism reports · 2022Article
- Noncovalent Enzyme Nanogels via a Photocleavable Linkage.Macromolecules · 2022Article
- Lipid nanoparticle delivers phenylalanine ammonia lyase mRNA to the liver leading to catabolism and clearance of phenylalanine in a phenylketonuria mouse model.Molecular genetics and metabolism reports · 2022Article
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundThis study assessed the immunogenicity of pegvaliase (recombinant Anabaena variabilis phenylalanine [Phe] ammonia lyase [PAL] conjugated with polyethylene glycol [PEG]) treatment in adults with phenylketonuria (PKU) and its impact on safety and efficacy.
methodsImmunogenicity was assessed during induction, upward titration, and maintenance dosing regimens in adults with PKU (n = 261). Total antidrug antibodies (ADA), neutralizing antibodies, immunoglobulin (Ig) M and IgG antibodies against PAL and PEG, IgG and IgM circulating immune complex (CIC) levels, complement components 3 and 4 (C3/C4), plasma Phe, and safety were assessed at baseline and throughout the study. Pegvaliase-specific IgE levels were measured in patients after hypersensitivity adverse events (HAE).
findingsAll 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.
interpretationDespite 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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.