Clinical Data

Results of clinical trials showed efficacy of KUVAN® (sapropterin dihydrochloride) in reducing blood phenylalanine (Phe) levels and increasing dietary Phe tolerance.1



Clinical Data


Results of clinical trials demonstrated the efficacy of KUVAN® to reduce blood Phe levels and to increase dietary Phe tolerance.1

PKU-001 was a multicentre, open-label, uncontrolled clinical trial of 489 PKU patients aged 8-48 years who had baseline blood Phe levels ≥450μmol/L and were to receive KUVAN® 10mg/kg/day for 8 days; while PKU-003 was a multicentre, double-blind, placebo-controlled trial of PKU patients who responded to KUVAN® in PKU-001. After a washout period from PKU-001, patients were randomised equally for 6-week treatment with KUVAN® 10mg/kg/day or placebo.1

The results showed that:1

  • KUVAN® 10mg/kg/day significantly reduced blood Phe levels as compared to placebo.
  • The baseline blood Phe levels for the KUVAN®-treated group and the placebo group were similar, with mean (±SD) baseline blood Phe levels of 843 (±300) μmol/L and 888 (±323) μmol/L, respectively.
  • The mean (±SD) decrease from baseline in blood Phe levels at the end of the 6 week study period was 236 (±257) μmol/L for the KUVAN® treated group as compared to an increase of 3 (±240) μmol/L for the placebo group (p<0.001)

For patients with baseline blood Phe levels ≥600μmol/L, 42% (13/31) of those treated with KUVAN® and 13% (5/38) of those treated with placebo had blood Phe levels <600μmol/L at the end of the 6-week study period (p=0.012).

Long-term blood Phe levels control2

Long-term efficacy of KUVAN® was demonstrated in the Phenylketonuria Demographic, Outcomes, and Safety (PKUDOS) Registry, a noncontrolled, open-label, observation study. It is found that KUVAN® increased Phe tolerance in responsive children and adults, permitting more natural protein in the diet.

Key results:

  • There was a significant and persistent decrease in blood Phe levels
  • The mean of median blood Phe levels decrease of 43% was sustained over 5 years
Reduction of Blood Phe Levels in BH4-Responsive Patients1,3

PKU-003 was a pivotal phase 3, multicentre, double-blind, placebo-controlled study of 88 patients with PKU, aged 8-49 years. About 44% of patients in the KUVAN® group saw reduction in blood Phe levels of 30% or greater vs. 9% in the placebo group.

Paediatric population

In a multicentre, open-label randomised, controlled study (SPARK), 56 paediatric PKU patients <4 years of age were randomised 1:1 to receive either sapropterin dihydrochloride 10 mg/kg/day plus a Phe-restricted diet (n=27), or just a Phe-restricted diet (n=29) over a 26-week study period.1

The results demonstrated that daily dosing with sapropterin dihydrochloride 10 or 20mg/kg/day plus Phe-restricted diet led to statistically significant improvements in dietary Phe tolerance compared with dietary Phe restriction alone while maintaining blood Phe levels within the target range (≥120 to <360µmol/L).1

Adverse events1,4

In clinical trials, KUVAN® has been administered to 579 PKU patients aged 4-48 years in doses ranging from 5-20mg/kg/day for treatment durations from 1 week to 3 years.

Results showed that about 35% of participants experienced adverse events, and the overall incidence of adverse events in patients receiving KUVAN® was similar to the placebo group. The most commonly reported adverse reactions are headache, upper respiratory tract infection, and rhinorrhoea.1

KUVAN® has an acceptable safety profile in both adults and children.1

In the SPARK study, 29.6% of the 27 children aged <4 years who received KUVAN® dosages of 10 or 20mg/kg/day plus Phe-restricted diet experienced AEs.4

Please refer to KUVAN® Product Information for further information on clinical trials.


  1. KUVAN® Product Information.
  2. Longo N, et al. Mol Genet Metab. 2015;114(4):557-563.
  3. Levy HL, et al. Lancet. 2007;370(9586):504-510.
  4. Muntau A, et al. Orphanet J Pare Dis. 2017;12(1):47.