Long-Term Safety and Efficacy of Pegvaliase in Japanese Adults With Phenylketonuria: Final Results of a Phase III Trial.

Phenylketonuria (PKU) is an inborn error of metabolism leading to phenylalanine (Phe) accumulation and consequent neurological, neurocognitive, and psychiatric symptoms. Pegvaliase, a pegylated recombinant phenylalanine ammonia lyase that metabolizes Phe, effectively reduced blood Phe in phase III studies in the United States. This multicenter, open-label, phase III study (jRCT2080224573) evaluated efficacy and safety of up to 4 years of pegvaliase treatment in 12 adult Japanese participants with PKU (blood Phe > 600 μmol/L). Subcutaneous pegvaliase followed an induction/titration/maintenance dosing regimen up to a maximum of 60 mg/day. After Week 52, diet and pegvaliase dose could be adjusted if blood Phe was ≤ 360 μmol/L. Mean (standard deviation [SD]) treatment duration was 166.4 (66.5) weeks. At Week 192 (n = 10), mean (SD) blood Phe was 296.2 (430.7) μmol/L, a 71.2% decrease from baseline, and daily protein intake from intact and medical food was 49.9 (21.4) g (68.0% increase) and 7.6 (16.2) g (64.2% decrease), respectively. All participants had ≥ 1 treatment-emergent adverse event (TEAE) during induction/titration, most commonly injection site erythema and injection site swelling (83.3% each); nine of 10 had a TEAE during maintenance. Of 395 TEAEs recorded during maintenance, 82 occurred between the 2-year interim analysis and the 4-year final analysis. One serious TEAE (allergic arthritis) was considered pegvaliase related. The exposure-adjusted rate of pegvaliase-related events was 17.0 per person-year (41.2 during induction/titration, 8.9 during maintenance). Pegvaliase effectively lowered blood Phe in Japanese participants with PKU, with no new safety issues with long-term treatment, and many participants were able to liberalize their diet.