udy 2
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