Pegvaliase dose escalation to 80 mg daily may lead to efficacy in patients who do not exhibit an optimal response at lower doses
In 2018, pegvaliase was approved as the first enzyme substitution treatment for phenylketonuria (PKU) and is now the second medication available for PKU patients since the approval of sapropterin dihydrochloride in 2007. Historically, dietary management has been the mainstay of treatment for PKU. Wh...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Molecular Genetics and Metabolism Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426922000659 |
| _version_ | 1811339907952541696 |
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| author | Erika R. Vucko Kirsten E. Havens Joshua J. Baker Barbara K. Burton |
| author_facet | Erika R. Vucko Kirsten E. Havens Joshua J. Baker Barbara K. Burton |
| author_sort | Erika R. Vucko |
| collection | DOAJ |
| description | In 2018, pegvaliase was approved as the first enzyme substitution treatment for phenylketonuria (PKU) and is now the second medication available for PKU patients since the approval of sapropterin dihydrochloride in 2007. Historically, dietary management has been the mainstay of treatment for PKU. While sapropterin response rate is limited to approximately 50% of PKU patients, pegvaliase has the potential to reduce phenylalanine levels in all PKU patients (Vockley et al., 2014; Longo et al., 2019 [1,3]). Current FDA labeling for pegvaliase includes a dose maximum of 60 mg daily (Longo et al., 2019; BioMarin Pharmaceutical Inc., 2020 [3,4]). We report a case series of four phenylalanine hydroxylase (PAH) deficient patients, previously treated with dietary management only, who initiated treatment with pegvaliase and were titrated to 80 mg daily dosing. The safety profile in these four cases did not differ from lower maintenance dosing (Longo et al., 2019 [3]). Subsequent decreases in Phe levels were observed on 80 mg maintenance dosing, allowing for individualized dietary liberalization in three out of four patients. We conclude that pegvaliase dosing must be personalized to achieve therapeutic goals and that some patients may require higher doses than those included on the product label. |
| first_indexed | 2024-04-13T18:33:24Z |
| format | Article |
| id | doaj.art-97304287bfbb43ccb35c7420da338278 |
| institution | Directory Open Access Journal |
| issn | 2214-4269 |
| language | English |
| last_indexed | 2024-04-13T18:33:24Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj.art-97304287bfbb43ccb35c7420da3382782022-12-22T02:34:58ZengElsevierMolecular Genetics and Metabolism Reports2214-42692022-09-0132100905Pegvaliase dose escalation to 80 mg daily may lead to efficacy in patients who do not exhibit an optimal response at lower dosesErika R. Vucko0Kirsten E. Havens1Joshua J. Baker2Barbara K. Burton3Division of Genetics, Genomics, and Metabolism, Ann & Robert H. Lurie Children's Hospital, Chicago, IL, United States of America; Northwestern Feinberg School of Medicine, Chicago, IL, United States of America; Corresponding author at: Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago Avenue, Box 59, Chicago, IL 60611, United States of America.Division of Genetics, Genomics, and Metabolism, Ann & Robert H. Lurie Children's Hospital, Chicago, IL, United States of AmericaDivision of Genetics, Genomics, and Metabolism, Ann & Robert H. Lurie Children's Hospital, Chicago, IL, United States of America; Northwestern Feinberg School of Medicine, Chicago, IL, United States of AmericaDivision of Genetics, Genomics, and Metabolism, Ann & Robert H. Lurie Children's Hospital, Chicago, IL, United States of America; Northwestern Feinberg School of Medicine, Chicago, IL, United States of AmericaIn 2018, pegvaliase was approved as the first enzyme substitution treatment for phenylketonuria (PKU) and is now the second medication available for PKU patients since the approval of sapropterin dihydrochloride in 2007. Historically, dietary management has been the mainstay of treatment for PKU. While sapropterin response rate is limited to approximately 50% of PKU patients, pegvaliase has the potential to reduce phenylalanine levels in all PKU patients (Vockley et al., 2014; Longo et al., 2019 [1,3]). Current FDA labeling for pegvaliase includes a dose maximum of 60 mg daily (Longo et al., 2019; BioMarin Pharmaceutical Inc., 2020 [3,4]). We report a case series of four phenylalanine hydroxylase (PAH) deficient patients, previously treated with dietary management only, who initiated treatment with pegvaliase and were titrated to 80 mg daily dosing. The safety profile in these four cases did not differ from lower maintenance dosing (Longo et al., 2019 [3]). Subsequent decreases in Phe levels were observed on 80 mg maintenance dosing, allowing for individualized dietary liberalization in three out of four patients. We conclude that pegvaliase dosing must be personalized to achieve therapeutic goals and that some patients may require higher doses than those included on the product label.http://www.sciencedirect.com/science/article/pii/S2214426922000659PhenylketonuriaPegvaliaseDosing |
| spellingShingle | Erika R. Vucko Kirsten E. Havens Joshua J. Baker Barbara K. Burton Pegvaliase dose escalation to 80 mg daily may lead to efficacy in patients who do not exhibit an optimal response at lower doses Molecular Genetics and Metabolism Reports Phenylketonuria Pegvaliase Dosing |
| title | Pegvaliase dose escalation to 80 mg daily may lead to efficacy in patients who do not exhibit an optimal response at lower doses |
| title_full | Pegvaliase dose escalation to 80 mg daily may lead to efficacy in patients who do not exhibit an optimal response at lower doses |
| title_fullStr | Pegvaliase dose escalation to 80 mg daily may lead to efficacy in patients who do not exhibit an optimal response at lower doses |
| title_full_unstemmed | Pegvaliase dose escalation to 80 mg daily may lead to efficacy in patients who do not exhibit an optimal response at lower doses |
| title_short | Pegvaliase dose escalation to 80 mg daily may lead to efficacy in patients who do not exhibit an optimal response at lower doses |
| title_sort | pegvaliase dose escalation to 80 mg daily may lead to efficacy in patients who do not exhibit an optimal response at lower doses |
| topic | Phenylketonuria Pegvaliase Dosing |
| url | http://www.sciencedirect.com/science/article/pii/S2214426922000659 |
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