Pegvaliase Treatment for Adolescents With Phenylketonuria: A Multi-Site Study

Suzanne Hollander; Briana Valli; Erika Vucko; Melissa Lah; Amarilis Sanchez-Valle; Brittany M Murray; Amy Kritzer; Stephanie Sacharow

doi:10.1002/jmd2.70070

Pegvaliase Treatment for Adolescents With Phenylketonuria: A Multi-Site Study

JIMD Rep. 2026 Feb 17;67(2):e70070. doi: 10.1002/jmd2.70070. eCollection 2026 Mar.

Authors

Suzanne Hollander^{1

2}, Briana Valli^{1

3}, Erika Vucko⁴, Melissa Lah⁵, Amarilis Sanchez-Valle⁶, Brittany M Murray¹, Amy Kritzer^{1

7}, Stephanie Sacharow^{1

7}

Affiliations

¹ Division of Genetics and Genomics Boston Children's Hospital Boston Massachusetts USA.
² Department of Clinical Nutrition Boston Children's Hospital Boston Massachusetts USA.
³ Dr. Kiran C Patel College of Allopathic Medicine Nova Southeastern University Fort Lauderdale Florida USA.
⁴ Edwards Family Division of Genetics and Rare Diseases Lurie Children's Hospital Chicago Illinois USA.
⁵ Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA.
⁶ Department of Pediatrics, Division of Genetics and Metabolism University of South Florida Health Tampa Florida USA.
⁷ Department of Pediatrics Harvard Medical School Boston Massachusetts USA.

Abstract

Phenylketonuria (PKU) is an inherited metabolic disorder causing elevated phenylalanine (Phe) levels and neurocognitive impairment if left untreated. While dietary therapy remains the treatment standard, adherence declines during adolescence. Pegvaliase, an injectable enzyme therapy approved for adults > 18 years in the United States, lowers Phe levels while allowing dietary flexibility. This study examines pegvaliase use in adolescents, focusing on efficacy, discontinuation patterns, and predictors of success. We conducted a retrospective chart review from four metabolic centers with 53 individuals with PKU (age 14-22 years) who initiated pegvaliase through March 2025. Data included demographics, treatment response, side effects, and discontinuation reasons. Mean pretreatment Phe was 716 μmol/L, which decreased by 44% post-treatment initiation. Sixty-four percent of individuals achieved efficacy with a mean Phe of 231 μmol/L (60% decrease) after 14 months at mean dose of 37.4 mg/day. Common side effects included injection site reactions in 77%, joint pain in 64%, rash in 45%, headaches in 26%, fatigue in 19%, fever and/or chills in 13%, GI symptoms in 13%, and anaphylaxis in 9%. Discontinuation occurred in 24.5% of this cohort, with rates significantly higher in 12th graders (40%) and college students (32%) versus 9th-11th graders (5.5%). Pegvaliase may lower Phe levels in adolescents, reaching target blood Phe goals (≤ 360 μmol/L) once efficacy is achieved. Treatment showed better sustainability when initiated earlier in adolescence. The higher discontinuation during transitional years (12th grade/college) suggests treatment challenges increase during these periods. Earlier initiation, when family support is typically stronger, may improve outcomes. These findings support reconsidering current age restrictions for pegvaliase therapy.

Keywords: adherence; adolescents; pegvaliase; phenylalanine; phenylalanine ammonia‐lyase; phenylketonuria.