Department of Family Medicine and Community Health; Clinical Pharmacy Services; Commonwealth Medicine
Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Enzymes and Coenzymes | Medicinal and Pharmaceutical Chemistry | Nervous System Diseases | Nutritional and Metabolic Diseases | Therapeutics
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 micromol/L who have failed existing management strategies.
PKU, Palynziq, pegvaliase, pegvaliase-pqpz, phenylalanine ammonia lyase, phenylketonuria
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Copyright © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (http://www.uk.sagepub.com/aboutus/openaccess.htm).
DOI of Published Version
Drug Target Insights. 2019 Jun 21;13:1177392819857089. doi: 10.1177/1177392819857089. eCollection 2019. Link to article on publisher's site
Drug target insights
Hydery T, Coppenrath VA. (2019). A Comprehensive Review of Pegvaliase, an Enzyme Substitution Therapy for the Treatment of Phenylketonuria. Open Access Publications by UMMS Authors. https://doi.org/10.1177/1177392819857089. Retrieved from https://escholarship.umassmed.edu/oapubs/3877
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons, Enzymes and Coenzymes Commons, Medicinal and Pharmaceutical Chemistry Commons, Nervous System Diseases Commons, Nutritional and Metabolic Diseases Commons, Therapeutics Commons