UMMS Affiliation

Department of Family Medicine and Community Health; Clinical Pharmacy Services; Commonwealth Medicine

Publication Date

2019-06-21

Document Type

Article

Disciplines

Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Enzymes and Coenzymes | Medicinal and Pharmaceutical Chemistry | Nervous System Diseases | Nutritional and Metabolic Diseases | Therapeutics

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 micromol/L who have failed existing management strategies.

Keywords

PKU, Palynziq, pegvaliase, pegvaliase-pqpz, phenylalanine ammonia lyase, phenylketonuria

Rights and Permissions

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

10.1177/1177392819857089

Source

Drug Target Insights. 2019 Jun 21;13:1177392819857089. doi: 10.1177/1177392819857089. eCollection 2019. Link to article on publisher's site

Journal/Book/Conference Title

Drug target insights

Related Resources

Link to Article in PubMed

PubMed ID

31258325

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.