Induction, titration, and maintenance dosing regimen in a phase 2 study of pegvaliase for control of blood phenylalanine in adults with phenylketonuria

Molecular Genetics and Metabolism
Roberto ZoriNicola Longo

Abstract

Phenylketonuria (PKU) is caused by a deficiency in phenylalanine hydroxylase enzyme activity that leads to phenylalanine (Phe) accumulation in the blood and brain. Elevated blood Phe levels are associated with complications in adults, including neurological, psychiatric, and cognitive issues. Even with nutrition and pharmacological management, the majority of adults with PKU do not maintain blood Phe levels at or below guideline recommended levels. Pegvaliase, PEGylated recombinant Anabaena variabilis phenylalanine ammonia lyase (PAL), converts Phe to trans-cinnamic acid and ammonia, and is an investigational enzyme substitution therapy to lower blood Phe in adults with PKU. Pegvaliase was administered using an induction, titration, and maintenance dosing regimen in adults with PKU naïve to pegvaliase treatment. Doses were gradually increased until blood Phe ≤ 600 μmol/L was achieved. The maintenance dose was the dose at which participants achieved and sustained blood Phe ≤ 600 μmol/L for at least 4 weeks without dose modification. Analyses were performed for participants who achieved (Group A, n = 11) and did not achieve (Group B, n = 13) maintenance dose during the first 24 weeks of study treatment. Baseline mean blood Phe fo...Continue Reading

Citations

Oct 26, 2018·Nutritional Neuroscience·Penelope D Manta-VogliKleopatra H Schulpis
Mar 14, 2019·Drugs·Uta Lichter-Konecki, Jerry Vockley
Dec 14, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Nicola LongoCary O Harding
Apr 5, 2020·Orphanet Journal of Rare Diseases·Kimber van VlietM Rebecca Heiner-Fokkema
Jan 24, 2021·Nature Protocols·Erica L-W MajumderGary Siuzdak
Aug 26, 2021·Molecular Genetics and Metabolism Reports·Darius AdamsKaleigh Whitehall

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