Merck receives EU-approval to extend Kuvan use to children with PKU below age four

European Commission decision confirms earlier CHMP recommendation for change to product information

European Commission decision confirms earlier CHMP recommendation for change to product information

20150815ep30The European Commission (EC) has authorised a change to the European marketing authorisation for Merck’s product Kuvan (sapropterin dihydrochloride), to allow its use in children with phenylketonuria (PKU) below four years of age who have been shown to be responsive to such treatment. The EC decision follows the positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) in May 2015, which was based on a review of data from SPARK, a Phase IIIb clinical study. The EC decision is applicable to all 28 EU member states and the basis for corresponding decisions issued by Norway, Iceland and Liechtenstein.

“PKU is a rare disease with significant consequences — but if managed appropriately, it doesn’t have to impair child development or quality of life for children and adults. We are committed to helping patients with PKU, both at adult age and during childhood. The positive EC decision allows physicians to use Kuvan also in children right from diagnosis, who have shown to be responsive to the medication,” said Luciano Rossetti, Head of Global Research & Development at Merck’s biopharmaceutical business, Merck Serono.

Commenting on the news, Professor Dr Ania Carolina Muntau of the University Hospital Hamburg-Eppendorf, Hospital for Children and Youth Medicine, lead investigator of the SPARK study said, “It is a very positive development for children with PKU under the age of four who are suitable for the therapy. Managing PKU in young children through the maintenance of a phenylalanine-restricted diet alone is very challenging, and parents will welcome this approval, which could make the treatment easier. The evidence shows that Kuvan significantly improves tolerance to phenylalanine, allowing more flexibility in the management of the very restrictive diet in PKU patients.”

Detailed 26-week data from the SPARK study were presented at the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium in September 2014. Results showed that the addition of Kuvan to a phenylalanine-restricted diet significantly increased phenylalanine tolerance by 30.5 mg/kg/day in children with PKU below four years of age and responsive to Kuvan, when compared with phenylalanine tolerance in children following a phenylalanine-restricted diet alone (p<0.001). In the group treated with phenylalanine-restricted diet plus Kuvan phenylalanine tolerance was increased from 37.1 mg/kg/day at baseline to 80.6 mg/kg/day after 26 weeks, and in the phenylalanine-restricted diet alone from 35.8 mg/kg/day at baseline to 50.1 mg/kg/day after 26 weeks, respectively.

PKU is an inborn metabolic disorder that causes the toxic accumulation of phenylalanine, an essential amino acid contained in all protein-rich foods, in the brain and blood.1,2 Untreated, PKU can lead to intellectual disability, seizures and other serious medical problems.1,2 In many countries, implementation of national newborn screening programmes has allowed identification of children with PKU at birth, enabling the management of the disease to begin as early as possible in order to prevent potentially severe neurological damage.3 However, in Europe there has not been, to date, a licensed medication for the treatment of PKU in children who are below four years of age.

Following EC approval, the Summary of Product Characteristics (SmPC) will be updated to include details about the use of Kuvan in this younger population. It affects approximately 1/10,000 newborns in Europe.

The original European marketing authorisation for Kuvan was granted in 2008. In Europe, Kuvan was the first, and remains the only medication in combination with phenylalanine-restricted diet designed to reduce the concentration of phenylalanine in the blood and brain in those patients who are responsive to Kuvan to prevent the debilitating effects of PKU.4 Kuvan is already indicated in patients of all ages with tetrahydrobiopterin (BH4) deficiency, and in those aged four years and above with PKU (due to phenylalanine hydroxylase enzyme deficiency) who are responsive to Kuvan.


1. Blau N: Phenylketonuria and BH4 deficiencies. Bremen: Uni-Med; 2010
2. Blau N, van Spronsen FJ, Levy HL: Phenylketonuria. Lancet 2010,376:1417–1427
3. Loeber JG. Neonatal screening in Europe: the situation in 2004. J Inherit Metab Dis 2007;30:30–38
4., Accessed 15.06.2015

EP News BureauMumbai

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