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. 2026 Feb 8;147(4):109768.
doi: 10.1016/j.ymgme.2026.109768. Online ahead of print.

Management of pegvaliase-related skin concerns: best practice recommendations using a modified Delphi approach

Alvaro Hermida Ameijeiras  1 , Erika Vucko  2 , Cary O Harding  3 , Melissa Lah  4 , Ania Carolina Muntau  5 , Valentina Rovelli  6 , Janet A Thomas  7 , Sarah Rose  8 , Kristin Lindstrom  9 , Stephanie Sacharow  10
Affiliations
Free article

Management of pegvaliase-related skin concerns: best practice recommendations using a modified Delphi approach

Alvaro Hermida Ameijeiras et al. Mol Genet Metab. .
Free article

Abstract

Introduction: The approval of pegvaliase (PALYNZIQ®) represented a paradigm shift in the management of phenylketonuria (PKU) by enabling sustained reductions in blood phenylalanine levels and permitting an unrestricted diet. However, as it is a bacterially derived injectable therapy, individuals receiving pegvaliase may experience skin-related adverse events (AEs). Anticipating these AEs and other pegvaliase-related skin concerns and having best-practice strategies to manage them may be crucial to achieving optimal patient outcomes.

Methods: An expert panel comprising eight clinicians from the USA and Europe convened to develop best practice recommendations for managing pegvaliase-associated skin concerns. Employing a modified Delphi process, the panel generated 39 initial statements based on their clinical insights and results of a targeted literature review. These statements were refined over two phases of anonymous voting using a 10-point scale, with consensus predefined as ≥75% of panellists rating a statement ≥7.

Results: The Delphi process resulted in 18 consensus statements. These were organized into three themes: patient-centric recommendations/considerations; considerations for premedications and concomitant medications; and recommendations for monitoring. Key recommendations included comprehensive patient education to overcome needle phobia and promote self-injection; training on injection technique and rotation to reduce scar tissue formation; and the proactive use of premedications and as-needed concomitant medications to mitigate skin reactions. Recommendations also emphasize the importance of regular in-person follow-up to assess injection sites and monitor for scar tissue. Mean agreement scores ranged from 8.5 to 10, reflecting robust consensus among panel members.

Conclusions: These internationally relevant, evidence-based recommendations provide a structured framework for managing pegvaliase-related skin concerns. Adoption of this guidance may enhance treatment adherence, mitigate adverse events, and ultimately improve patient outcomes.

Keywords: Modified Delphi; Patient-centric care; Pegvaliase; Phenylketonuria; Recommendations; Skin reactions.

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Conflict of interest statement

Declaration of competing interest AHA has participated as a clinical trial investigator for Ultragenyx; received consulting payments from Amicus Therapeutics, BioMarin, Chiesi, Genzyme, PTC Therapeutics, Shire, and Ultragenyx; speaker fees from Alexion, Amicus Therapeutics, BioMarin, Genzyme, InMedica, Nutricia, Sobi, Takeda, and Vitaflo; and travel support from Amicus Therapeutics, BioMarin, Chiesi, Genzyme, InMedica, Sobi, and Vitaflo. EV has participated as a clinical trial investigator for BioMarin and Otsuka; received consulting payments from BioMarin, PTC Therapeutics, and Horizon/Amgen; speaker fees from BioMarin, Horizon/Amgen, and PTC Therapeutics; and travel support from BioMarin. COH has participated as a clinical trial investigator for and received consulting payments, speaker fees, and travel support from BioMarin. ML has participated as a clinical trial investigator for BioMarin, PTC Therapeutics, Synlogic Therapeutics, and Homology Medicines; received consulting payments from BioMarin, PTC Therapeutics, and Travere Therapeutics; and travel support from BioMarin. ACM has participated as a clinical trial investigator for PTC Therapeutics and BioMarin; received consulting payments from Atheneum, PTC Therapeutics, BioMarin, Jnana Therapeutics, and Pluvia; speaker fees from AIM, Applied Pharma Research, PTC Therapeutics, and BioMarin; and travel support from PTC Therapeutics and BioMarin. VR has received consulting payments from BioMarin, PTC Therapeutics, DMF Pharma, Dipharma, and Mamoxi SrL; and travel support from BioMarin. JAT has participated as a clinical trial investigator for PTC Therapeutics, BioMarin, Sanofi, Travere Therapeutics, and Ultragenyx; received consulting payments from BioMarin and Travere Therapeutics; and travel support from BioMarin and Travere Therapeutics. SR and KL are employees and shareholders of BioMarin. SS has received consulting payments from PTC Therapeutics and Jnana Therapeutics; and travel support from BioMarin and PTC Therapeutics. In addition, SS's institution has received research grants from BioMarin; payments for SS participating as a clinical trial investigator for BioMarin, PTC Therapeutics, Jnana Therapeutics, and Synlogic; and payment from BioMarin for SS acting as a consultant and a speaker.

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