Hyperphenylalaninemia in Phenylketonuria Drug Approved

Merck Serono, a division of Merck KGaA, has received marketing authorization from the European Commission for Kuvan for the treatment of hyperphenylalaninemia (HPA) in phenylketonuria (PKU) or BH4 deficient patients. Kuvan, which had previously received Orphan Medicinal Product designation from the European Medicines Evaluation Agency (EMEA), is the first drug approved in Europe for HPA due to PKU or BH4 deficiency.

“To date, there has been no drug treatment available in Europe for patients suffering from PKU, a debilitating inherited condition that can cause serious brain damage in children and transient to lasting impairments in adults if a strict diet is not observed throughout life,” said Roberto Gradnik, executive vice president Commercial Europe at Merck Serono. “With the approval of Kuvan, Merck Serono provides patients access to an efficient treatment to better control their blood phenylalanine levels. This will contribute to improving their quality of life and may ultimately reduce the risk of lasting mental impairment.”

There are approximately 35,000 patients diagnosed with hyperphenylalaninemia due to PKU or BH4 deficiency in the EU. PKU and BH4 deficiency are rare diseases caused by genetic defects in the metabolism of the amino acid phenylalanine (PKU), or in the enzymes responsible for the recycling and synthesis of the cofactor BH4 (BH4 deficiency), resulting in hyperphenylalaninemia, i.e. abnormally high levels of phenylalanine in the blood. Hyperphenylalaninemia can cause serious brain damage in infants and children, and transient to lasting neurocognitive impairment in adult patients.

Previously, the only therapy option for PKU patients in Europe to manage their disease was through a diet highly restricted in phenylalanine (food with high levels of phenylalanine include meat, fish, nuts, dairy products and some vegetable and fruits) associated with daily amino-acid supplementation. Non-adherence to the restrictive diet and adequate control of blood phenylalanine levels can result in a decline in mental and behavioral performance.

The marketing authorization is supported by data from two international, double-blind, randomized, placebo-controlled Phase III clinical trials in patients with hyperphenylalaninemia due to PKU. The data show that treatment with Kuvan reduces blood phenylalanine levels and increases the proportion of patients with blood phenylalanine levels within target range, resulting in a higher dietary phenylalanine tolerance, which may reduce the need to limit phenylalanine intake in patients’ diet.

As an Orphan Medicinal Product and the first drug approved for the treatment of HPA, Kuvan will receive 10 years of data protection in the European Union for this therapeutic indication. Launch of Kuvan in Europe is expected to start in the first half of 2009.