Pegvaliase therapy for phenylketonuria: Real-world case series and clinical insights

Iris Scala; Lucia Brodosi; Daniela Gueraldi; Filippo Manti; Valentina Rovelli; Juri Zuvadelli; Giulio Agnelli; Chiara Cazzorla; Francesca Nardecchia; Antonina Giammanco; Giacomo Biasucci

doi:10.1016/j.ymgme.2024.108151

Pegvaliase therapy for phenylketonuria: Real-world case series and clinical insights

Mol Genet Metab. 2024 Feb 2;142(1):108151. doi: 10.1016/j.ymgme.2024.108151. Online ahead of print.

Authors

Affiliations

¹ Clinical Genetics Unit, Department of Maternal and Child Health, Federico II University Hospital, Naples, Italy.
² Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Clinical Nutrition and Metabolism Unit, IRCCS AOUBO, Bologna, Italy. Electronic address: luciabrodosi@gmail.com.
³ Division of Inherited Metabolic Diseases, Department of Women's and Children's Health, University Hospital of Padova, Padova, Italy.
⁴ Unit of Child Neurology and Psychiatry, Department of Human Neuroscience, University of Rome La Sapienza, Rome, Italy.
⁵ Clinical Department of Pediatrics, San Paolo Hospital, ASST Santi Paolo e Carlo, University of Milan, Italy.
⁶ Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
⁷ Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.
⁸ Pediatrics & Neonatology Unit, Guglielmo da Saliceto Hospital, Piacenza, Italy; Department of Medicine and Surgery, University of Parma, Parma, Italy.

PMID: 38522180
DOI: 10.1016/j.ymgme.2024.108151

Abstract

Objective: The aim of this study is to present a series of case studies on the real-life use of pegvaliase in Italy in managing patients affected by phenylketonuria (PKU) and provide practical insight and support to healthcare professionals currently approaching and facing this novel enzyme substitution therapy.

Methods: A panel of 11 PKU experts from seven leading Italian treatment centers attended online virtual meetings with the aim of reviewing their clinical and practical experiences with pegvaliase based on occurred cases. In selecting the cases, specific consideration was given to the nationwide representation of the centers involved and to the number of patients with PKU managed. Cases were thoroughly reviewed, with comprehensive discussions enabling the identification of key take-home messages regarding pegvaliase therapy.

Results: The panel discussed 18 cases, 11 males and 7 females (age range 17-43 years). At the last follow-up (up to 111 weeks after pegvaliase initiation), 11 out of 18 patients (61%) reached Phe levels below 600 μmol/l. Outcomes varied significantly across cases. All cases underscore the potential of pegvaliase in reducing Phe levels, enhancing the quality of life, and promoting social skills and independence. Additionally, the cases highlight the challenges associated with pegvaliase therapy, including managing adverse events and ensuring patient motivation and adherence.

Conclusion: This is the first report about the Italian experience of managing patients affected by PKU with pegvaliase. Given the limited real-world data on the use of pegvaliase in PKU management, this case series offers valuable insights into the practical implementation and management of pegvaliase therapy in this Country. Continued research and data collection will be crucial to confirm and progress with this treatment. Despite potential challenges, pegvaliase therapy represents a substantial promise in managing PKU in Italy. Patient education, personalized treatment approaches, and careful monitoring are important to ensure optimal patient outcomes.

Keywords: Adverse events; Enzymatic therapy; Enzyme replacement therapy; PEGylated phenylalanine ammonia-lyase; PKU; Pegvaliase; Phenylketonuria; Therapy.