Clinical Data
This is the first placebo controlled study demonstrating the ability to improve Phe levels in PKU patients who at baseline do not have to follow a Phe-restricted diet. Typically, a Phe-restricted diet does not allow any protein intake outside of medical food. Patients in the trial were estimated to be eating 75% of the daily recommended allowance for protein intake for a healthy adult.In the secondary endpoints of the 8 week RDT, no benefit in inattention or mood scores were observed in patients treated with pegvaliase compared to placebo.  In an exploratory sub study of cognitive function in 9 patients, the Cambridge Neuropsychological Test Automated Battery (CANTAB) showed trends of improvement favoring pegvaliase. (see Table 2)In contrast to the short term results of the RDT, supportive evidence of the association of reduced blood Phe and improvement in inattentiveness comes from two long term evaluations in the PRISM-1 and PRISM-2 studies. In these studies, ADHD-RS assessments were obtained prior to treatment and at various times thereafter (scale range 0-27 points, higher score indicating greater impairment). In the open label PRISM-1 study (formerly referred to as 165-301 or feeder study), 49 patients had baseline inattention scores greater than 9 (defining patients with inattentive symptoms at baseline). Of the 35 patients whose Phe was reduced during PRISM-1 by greater than 20%, the mean improvement in inattention was 7.3 points, while the 14 patients whose Phe was reduced by less than 20% only showed an improvement of 3.7. (see Table 3).In the PRISM-2 study, the 72 patients were evaluated regardless of the baseline scores. Among those who completed 41 weeks in the open-label extension, patients were divided into quartiles based on the magnitude of their Phe reduction from baseline. The quartile of patients having the largest Phe reductions (to values lower than ≥ 1,296 umol/L) had mean improvements in their ADHD-RS inattention score of 7.5 while the patients with the smallest Phe reductions (to values no less than <289 umol/L) had mean improvements in the inattention score of 3.2. (See Table 4).