Depletion of interfering IgG and IgM is critical to determine the role of IgE in pegvaliase-associated hypersensitivity

摘要

Pegvaliase is an enzyme substitution therapy developed to lower blood phenylalanine (Phe) in adults with phenylketonuria (PKU). In phase 3 clinical studies, pegvaliase substantially reduced mean blood Phe in adult subjects with PKU. The most common type of adverse event observed in the pegvaliase clinical program was hypersensitivity adverse events (HAEs), which included occurrences of arthralgia, rash, and pruritis. The most clinically relevant HAEs were acute systemic hypersensitivity reactions consistent with anaphylaxis observed in 4.6% of phase 3 patients. HAEs were more commonly observed around the time of high circulating immune complex (CIC) levels and complement activation, and the majority of subjects that experienced acute systemic hypersensitivity events were able to continue treatment, which is atypical for a classical IgE-mediated anaphylactic event, but common for type III hypersensitivity reactions.