KUVAN is the first and only prescription medication indicated to lower blood Phe levels in patients with HPA due to BH4-responsive PKU. In BH4-responsive PKU patients, KUVAN was proven to lower their blood Phe levels.¹

• KUVAN is a novel treatment for PKU that targets the underlying enzymatic defect
• KUVAN lowers Phe levels in patients across the spectrum of PKU

The efficacy and safety of KUVAN were evaluated in 4 clinical studies in patients with PKU.

Responders to KUVAN

In a Phase 2, multicenter study to evaluate response to an 8-day course of
10 mg/kg/day KUVAN, 489 subjects were enrolled who had blood Phe levels
≥450 μmol/L, and were not on a Phe-restricted diet. Responders to KUVAN, defined as a ≥30% decrease in blood Phe levels from Day 1 to Day 8, were enrolled into Study 2.¹

KUVAN reduced blood Phe levels in patients who were not following a Phe-restricted diet

In a Phase 3, multicenter, double-blind, placebo-controlled study of 88 patients with PKU, aged 8 to 49 years who had elevated blood Phe levels (≥450 μmol/L) at screening and who responded to KUVAN in a previous study, patients were randomized to receive KUVAN at 10 mg/kg/day for 6 weeks (n=41) or a corresponding placebo (n=47).¹

*In a 6-week, Phase 3, multicenter, randomized, double-blind, placebo-controlled study of 88 patients who were responders to KUVAN. Patients continued their diet throughout the study. Treatment with KUVAN or placebo started at Week 0.¹
†P<0.001 for difference in mean blood Phe between groups at Week 6.¹

• KUVAN (10 mg/kg/day) reduced blood Phe by 29% after 6 weeks compared to a mean increase of 3% in the placebo group²⁶
  • The KUVAN group had a mean baseline (±SD) of 842.7±299.6 μmol/L (14.0 mg/dL),^‡ with a Phe level range at baseline of 293–1643 μmol/L (4.9–27.4 mg/dL)
  • The placebo group had a mean baseline (±SD) of 888.3±323.1 μmol/L (14.8 mg/dL),^‡ with a Phe level range at baseline of 402–1745 μmol/L (6.7–29.1 mg/dL)

^‡The mean baseline Phe levels represent the mean of 3 pretreatment levels (Week –2, Week –1, and Week 0).

KUVAN improves Phe control by complementing a low-Phe diet

In the second Phase 3, multicenter, randomized, double-blind, placebo-controlled study, 45 patients aged 4–12 years who had responded to KUVAN treatment earlier (n=33) were randomized to receive KUVAN 20 mg/kg/day. At baseline, the mean blood Phe level in the KUVAN group (pretreatment) was 276 μmol/L and the mean blood Phe level in the placebo group was 326 μmol/L.²⁶

*Patients who responded to KUVAN 20 mg/kg/day were randomized to receive KUVAN 20 mg/kg/day (n=33) or placebo (n=12). Patients were aged 4–12 years and were required to have Phe levels ≤480 μmol/L at screening. Patients remained on a Phe-restricted diet during the study and completed weekly 3-day diet records to confirm compliance.²⁶
†P<0.001 for change in mean blood Phe level from Week 0 to Week 3 within KUVAN group.²⁶

At Week 3, the mean blood Phe level of patients receiving KUVAN was 127 μmol/L compared to 230 μmol/L in the placebo group. The Phe drop in the KUVAN group was statistically significant (P<0.001).²⁶

• KUVAN (20 mg/kg/day) reduced blood Phe by 149 μmol/L from Week 0 to Week 3 (P<0.001) in patients as young as 4 years of age²⁶
• Reduction in blood Phe was apparent at the first posttreatment evaluation at Week 1 and was maintained over subsequent weeks²⁶

KUVAN works to keep the amount of Phe in the blood low week after week

In part 1 of a Phase 3 study evaluating long-term treatment for 22 weeks, patients received KUVAN in 3 consecutive 2-week courses of 5 mg/kg/day, followed by 20 mg/kg/day, and finally 10 mg/kg/day. Following this 6-week forced dose-titration period, patients continue to receive 10 mg/kg/day for 4 more weeks. In part 2 of this study, based on each patient’s blood Phe results from Weeks 2 and 6, patients were assigned 5, 10, or 20 mg/kg/day from Weeks 12 to 22. The baseline blood Phe level at Week 0 (mean±SD) was 844.0±398.0 μmol/L, and patients were instructed to continue their usual diet without modification throughout the study.²⁶

• In this study, higher doses of KUVAN produced greater decreases in Phe levels, with the largest drop in blood Phe level with the 20 mg/kg/day dose. The percentage of patients with ≥30% reduction in blood Phe levels were 25%, 46%, and 55% after dosing for 2 weeks with 5, 10, and 20 mg/kg/day, respectively²⁶
  • Treatment with KUVAN can reduce and sustain reduced blood
    Phe levels over a period of 22 weeks, with no indication that tolerance develops to KUVAN
  • Daily doses of KUVAN 5, 10, or 20 mg/kg/day were well tolerated over 22 weeks

*Patients (N=80) were ≥8 years of age, received ≥80% of KUVAN or placebo doses during 6 weeks of treatment in a previous Phase 3 study, had a baseline blood Phe level ≥450 μmol/L to enter the previous study, and continued their usual diet throughout both studies.²⁶