Clinical experience with Pegvaliase in phenylketonuria: A retrospective chart review of outcomes, safety, and dosing patterns

Background: Phenylketonuria (PKU) is a metabolic disorder caused by phenylalanine hydroxylase (PAH) deficiency, resulting in elevated plasma phenylalanine (Phe) levels. Pegvaliase (Palynziq®), pegylated phenylalanine ammonia lyase (PAL), was approved in 2018 to manage Phe levels in adults with PKU. Real-world data on its long-term efficacy and safety are limited. Objective: To evaluate clinical outcomes, dosing patterns, metabolic control, dietary modifications, and safety of pegvaliase treatment in PKU patients. Methods: A retrospective review was conducted on 37 PKU patients treated with pegvaliase between October 2018 and June 2025. Data included demographics, BH4 responsiveness, plasma Phe levels, dosing of pegvaliase, dietary intake, and adverse events (AEs). Results: Of 33 patients with sufficient follow-up, 24 (73%) achieved plasma Phe levels below 360 μmol/L at a mean of 264 ± 199 days. Within 24 months 85% of patients, including both BH4 (sapropterin) responders and non-responders, achieved two consecutive plasma Phe measurements below 360 μmol/L. Dose requirements varied with most patients achieving these target levels on daily pegvaliase injections ranging from 20 to 60 mg. Dietary liberalization was observed with the majority of patients discontinuing medical formula and reaching the protein Dietary Reference Intake (DRI) within roughly 12 months after initiating pegvaliase. Adverse events (AEs) occurred in 88.6% of patients, most commonly injection site reactions, arthralgia, and rashes of varying severity. Six patients experienced anaphylaxis, but none required hospitalization. Conclusions: Pegvaliase effectively improves metabolic control and dietary flexibility in adolescents and adults with PKU, promoting improved nutrition and overall quality of life. Individualized dosing and careful monitoring are essential due to variability in response and frequent AEs.