Sapropterin (N=41)
 Placebo (N=47)
 
Baseline Blood Phe Level* (μmol/L)
 
Mean (±SD)
 843 (±300)
 888 (±323)
 
Percentiles (25th, 75th)
 620, 990
 618, 1141
 
Week 6 Blood Phe Level (μmol/L)
 
Mean (±SD)
 607 (±377)
 891 (±348)
 
Percentiles (25th, 75th)
 307, 812
 619, 1143
 
Mean Change in Blood Phe From Baseline to Week 6 (μmol/L)
 
Adjusted Mean (±SE)†
 -239 (±38)
 6 (±36)
 
Percentiles (25th, 75th)
 -397, -92
 -96, 93
 
Mean Percent Change in Blood Phe From Baseline to Week 6
 
Mean (±SD)
 - 29 (±32)
 3 (±33)
 
Percentiles (25th, 75th)
 -61, -11
 -13, 12
 
*The mean baseline levels shown in this table represent the mean of 3 pretreatment levels (Wk -2, Wk -1, and Wk 0). Treatment with Kuvan or placebo started at Wk 0.

†p-value < 0.001, adjusted mean and standard error from an ANCOVA model with change in blood Phe level from baseline to Week 6 as the response variable, and both treatment group and baseline blood Phe level as covariates.

Change in blood Phe was noted in the Kuvan-treated group at Week 1 and was sustained through Week 6 (Figure 2).

Figure 2

Study 3 was a multicenter, open-label, extension study in which 80 patients who responded to Kuvan treatment in Study 1 and completed Study 2 underwent 6 weeks of forced dose-titration with 3 different doses of Kuvan. Treatments consisted of 3 consecutive 2-week courses of Kuvan at doses of 5, then 20, and then 10 mg/kg per day. Blood Phe level was monitored after 2 weeks of treatment at each dose level. At baseline, mean (±SD) blood Phe was 844 (±398) μmol/L. At the end of treatment with 5, 10, and 20 mg/kg per day, mean (±SD) blood Phe levels were 744 (±384) μmol/L, 640 (±382) μmol/L, and 581 (±399) μmol/L, respectively (Table 6).

Table 6: Blood Phe Results From Forced Dose-Titration in Study 3

Kuvan Dose Level (mg/kg per day)
 No. of Patients
 Mean (±SD) Blood Phe Level (μmol/L)
 Mean Changes (±SD) in Blood Phe Level From Week 0 (μmol/L)
 
Baseline

(No Treatment)
 80
 844 (±398)
 —
 
5
 80
 744 (±384)
 ‑100 (±295)
 
10
 80
 640 (±382)
 ‑204 (±303)
 
20
 80
 581 (±399)
 -263 (±318)
 
Study 4 was a multicenter study of 90 pediatric patients with PKU, ages 4 to 12 years, who were on Phe‑restricted diets and who had blood Phe levels ≤480 μmol/L at screening. All patients were treated with open-label Kuvan 20 mg/kg per day for 8 days. Response to Kuvan was defined as a ≥30% decrease in blood Phe from baseline at Day 8. At Day 8, 50 patients (56%) had a ≥30% decrease in blood Phe.

Study 5 was an open label, single arm, multicenter trial in 93 pediatric patients with PKU, aged 1 month to 6 years, who had Phe levels greater than or equal to 360 μmol/L at screening.   All patients were treat