In this expert-led discussion, the faculty examine how advances in rational drug design are translating into meaningful clinical impact, with a particular focus on pegunigalsidase alfa and its emerging role in patient care for Fabry disease.
João Gonçalves, PhD (Faculty of Pharmacy, University of Lisbon), Derralynn Hughes, BM BCh (Professor of Experimental Hematology, Lysosomal Disorders Unit, Royal Free London NHS Foundation Trust and University College London), and Eric Wallace, MD (Professor of Medicine, The University of Alabama at Birmingham) come together to discuss the evolving treatment landscape.
Fabry disease is a rare, progressive lysosomal disorder caused by α-galactosidase A deficiency, leading to multisystem involvement and significant clinical burden. Traditional enzyme replacement therapies (ERTs) for Fabry disease provide clinical benefit but remain limited by infusion burden, immunogenicity, and durability. Pegunigalsidase alfa is a next-generation ERT designed to address these challenges through PEGylation, extending half-life, enhancing stability, and supporting more consistent tissue exposure.
Professor João Gonçalves, Professor Derralynn Hughes, and Dr Eric Wallace explore the scientific principles and strategic approach to designing PEGylated enzyme replacement therapies. Panelists discussed the rational design of pegunigalsidase alfa, highlighting how PEGylation may impact enzyme stability, cellular uptake, and immunogenicity. Panelists further discussed this approach as a rational redesign rather than an incremental advance, with clinical and real-world data demonstrating sustained reductions in plasma lyso-Gb3, stabilization of renal function, and improved tolerability.
Building on this scientific foundation, presenters examined clinical and real-world data in patients with Fabry disease, interpreting observed outcomes in the context of rational PEGylation design. Immunogenicity and tolerability remain central to long-term management. Pegunigalsidase alfa may offer a more manageable immunogenicity profile, potentially improving treatment tolerability and durability.
The discussion also highlighted the importance of individualized management strategies, including supportive care and treatment switching for patients with suboptimal response to existing therapies. The symposium also featured patient case studies to bring the data to life and concluded with an interactive Q&A session.
This educational webinar is based on the presentation “Rational Design Meets Real-World Relevance: Pegunigalsidase Alfa in the Treatment of Fabry Disease” at the WORLDSymposium held in San Diego on February 4th, 2026. The program is sponsored by Chiesi Pharma Inc.