Merck Serono, a division of Merck KGaA, Darmstadt, Germany, today announced that the European Commission has granted marketing authorization for Kuvan(R) 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(R), 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," he added.
There are approximately 35,000 patients diagnosed with hyperphenylalaninemia due to PKU or BH4 deficiency in the European Union.(1) 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.
Until today, 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.
"Through the approval of Kuvan(R), Merck Serono confirms its commitment to developing and marketing innovative therapeutic solutions for patients suffering from high medical unmet needs. PKU and BH4 deficiency deserve the attention of the whole healthcare industry and we are pleased to provide patients today with the first therapeutic option to treat these rare diseases," said Richard Douge, Executive Vice President Global Marketing at Merck Serono.
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(R) 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. The most frequently reported potentially undesirable effects were headache, runny nose, diarrhea, vomiting, sore throat, cough, abdominal pain, stuffy nose and low levels of phenylalanine in the blood. These adverse events were generally mild to moderate and transient.
The European Commission has granted marketing authorization for the 27 countries(2) of the European Union as well as Iceland, Liechtenstein and Norway. As an Orphan Medicinal Product and the first drug approved for the treatment of HPA, Kuvan(R) will receive 10 years of data protection in the European Union for this therapeutic indication. Launch of Kuvan(R) in Europe is expected to start in the first half of 2009.
Kuvan(R)
Kuvan(R) (INN: sapropterin dihydrochloride, formerly known as Sapropterin and Phenoptin(TM)) is developed by Merck Serono and BioMarin Pharmaceutical Inc. (Nasdaq and SWX: BMRN) as an oral therapeutic for the treatment of hyperphenylalaninemia (HPA) due to phenylketonuria (PKU) or tetrahydrobiopterin (BH4) deficiency. Kuvan(R) is the synthetic form of 6R-BH4, a naturally occurring enzyme cofactor that works in conjunction with the enzyme phenylalanine hydroxylase (PAH) to metabolize phenylalanine (Phe). Clinical data suggest that Kuvan(R) produces significant reductions in blood Phe levels in the subset of patients who are BH4-responsive. Merck Serono estimates that Kuvan(R) could be a potential treatment option for the approximately 35,000 patients in the European Union who have been diagnosed with HPA, due to PKU or BH4 deficiency and are responsive to BH4 treatment.