Pegvaliase for the treatment of phenylketonuria: Final results of a long-term Phase 3 clinical trial program

Harding et al. investigated longer-term overall outcomes and characterized individual participant responses to pegvaliase from the randomized trials gathered from PRISM-1, PRISM-2 and the open-label extension study 165-304.

Pegvaliase treatment in individuals with phenylketonuria (PKU) resulted in substantial and sustained reductions in blood phenylalanine (Phe) levels, with clinically meaningful improvements observed across the long-term follow-up period. The majority of participants achieved blood Phe levels below clinically significant thresholds, with 71.3% reaching ≤600 µmol/L, 65.1% reaching ≤360 µmol/L, and 59.4% reaching ≤120 µmol/L. Safety data indicated that all participants (n=261) reported at least one adverse event (AE), with most being mild to moderate in severity. Despite the initial higher incidence of AEs in the early treatment phase, the overall safety profile improved with longer treatment duration.

The results of this study demonstrate that pegvaliase offers a significant and durable therapeutic benefit for managing blood Phe levels in PKU patients, accompanied by an acceptable safety profile.