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Review
. 2019 Jun 21:13:1177392819857089.
doi: 10.1177/1177392819857089. eCollection 2019.

A Comprehensive Review of Pegvaliase, an Enzyme Substitution Therapy for the Treatment of Phenylketonuria

Tasmina Hydery  1 , Valerie Azzopardi Coppenrath  2
Affiliations
Review

A Comprehensive Review of Pegvaliase, an Enzyme Substitution Therapy for the Treatment of Phenylketonuria

Tasmina Hydery et al. Drug Target Insights. .

Abstract

Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of a phenylalanine-metabolizing enzyme indicated to reduce blood phenylalanine concentrations, pegvaliase injection.

Data sources: Searches of MEDLINE (1946-September 1, 2018) were conducted using the terms pegvaliase and phenylalanine ammonia lyase (PAL). Additional data were obtained from the prescribing information, the product dossier obtained from the manufacturer, and Clinicaltrials.gov.

Study selection and data extraction: All English language articles related to pharmacology, pharmacokinetics, efficacy, or safety of the combination therapy in human subjects were reviewed.

Data synthesis: Pegvaliase is a pegylated PAL enzyme that converts phenylalanine to ammonia and trans-cinnamic acid. Blood phenylalanine levels were reduced by approximately 50% to 70% in patients receiving therapeutic doses of pegvaliase. However, most patients experienced adverse events.

Conclusions and relevance: The mainstay of therapy in phenylketonuria (PKU) has historically consisted of dietary restriction of phenylalanine. Pegvaliase injection is the first Food and Drug Administration (FDA)-approved enzyme substitution therapy for patients with PKU. The therapy may be a viable option for patients with documented blood phenylalanine >600 µmol/L who have failed existing management strategies.

Keywords: PKU; Palynziq; pegvaliase; pegvaliase-pqpz; phenylalanine ammonia lyase; phenylketonuria.

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Conflict of interest statement

Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

References

    1. National Institutes of Health Consensus Development Panel. National Institutes of Health Consensus Development Conference Statement: phenylketonuria: screening and management, October 16–18, 2000. Pediatrics 2001;108:972. - PubMed
    1. Bodamer OA, Hahn S, TePas E. Overview of phenylketonuria. In: Basow DS, ed. UpToDate [database on the internet]. Waltham, MA: UpToDate; 2018. http://www.utdol.com/utd/index.do. Accessed June 19, 2018.
    1. Scriver CR, Kaufman S. The hyperphenylalaninemias. Phenylalanine hydroxylase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001:1667.
    1. Vockley J, Andersson HC, Antshel KM, et al. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med. 2014;16:188–200. doi:10.1038/gim.2013.157. - DOI - PubMed
    1. Abadie V, Berthelot J, Feillet F, et al. [Management of phenylketonuria and hyperphenylalaninemia: the French guidelines]. Arch Pediatr. 2005;12:594. doi:10.1016/j.arcped.2005.02.004. - DOI - PubMed

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