Bratkovic D, Margvelashvili L, Tchan MC, et al. - In 24 adults with phenylketonuria (PKU) and hyperphenylalaninemia, PTC923 (sepiapterin) 60 mg/kg, PTC923 20 mg/kg and sapropterin 20 mg/kg were compared in a phase 2 randomized, multicenter, three-period crossover, open-label, active controlled, all-comers [regardless of phenylalanine hydroxylase variants] study.

• Adult men or women (18–60 y) with PKU were included and were administered 7 days of once-daily oral treatment with PTC923 20 mg/kg/day, PTC923 60 mg/kg/day and sapropterin dihydrochloride 20 mg/kg/day each in a random order.

• A significant decrease in blood phenylalanine (Phe) of participants with PKU was achieved with PTC923 treatment.

• Relative to baseline, least squares mean changes (SE) in blood Phe were: −206.4 (41.8) μmol/L for PTC923 60 mg/kg; −146.9 (41.8) μmol/L for PTC923 20 mg/kg; and − 91.5 (41.7) μmol/L for sapropterin.

• Significant more effectiveness of PTC923, vs sapropterin, in decreasing blood Phe was evident.

• Across all treatments, mild to moderate, transient, and similar adverse events were reported.

• PTC923 showed potential to serve as a new therapeutic choice for people with PKU.