Merck Serono Initiates Phase IIIb European Study SPARK in Children Younger Than Four Years, Suffering from Phenylketonuria

GENEVA, June 30, 2011 /PRNewswire/ --

Merck Serono, a division of Merck KGaA, Darmstadt, Germany, today announced the enrollment of the first patients in SPARK^[1]. The SPARK study will investigate the safety, efficacy and population pharmacokinetics of Kuvan^® (sapropterin dihydrochloride) in patients younger than four years, who suffer from Phenylketonuria (PKU).

PKU is a rare inborn metabolic disorder causing the toxic accumulation in brain and blood of an essential amino acid, Phenylalanine (Phe), found in all protein-containing foods. Until recently, the only way to prevent or reduce Phe blood level was a strict, life-long binding diet. In December 2008, Kuvan^® received a European marketing authorization in patients four years of age and older in PKU indication and in patients of all age in the indication of Tetrahydrobiopterin (BH4) deficiency.

"Beyond the implementation of SPARK as follow-up measure agreed with the European Medicines Agency, we want to make Kuvan^® available for patients who could benefit from it, including children younger than four years suffering from PKU", said Dr. Bernhard Kirschbaum, Executive Vice President Global Research and Development at Merck Serono.  

SPARK is a Phase IIIb, multi-center, open-label, randomized and controlled study that will be conducted in Europe and in Turkey. Fifty pediatric patients with PKU, younger than four years old, are expected to be included in SPARK. They will randomly receive either Kuvan^® therapy in conjunction with a Phe-restricted diet or the dietary therapy alone, over a period of 26 weeks.

Patients who complete the 26-weeks study period will be eligible to enter in an extension period, during which all subjects will undergo continued treatment with Kuvan^®, along with a Phe-restricted diet, over a period of up to three years.

^[1] SPARK: Safety Pediatric EfficAcy PhaRmacokinetic with Kuvan^® (sapropterin dihydrochloride).

About hyperphenylalaninemia (HPA)

Disorders of phenylalanine (Phe) metabolism can lead to abnormal elevations of blood Phe levels, also called hyperphenylalaninemia (HPA). Two inborn errors of metabolism, phenylketonuria (PKU) and tetrahydrobiopterin (BH4) deficiency, account for the majority of cases of HPA.

About phenylketonuria (PKU)

PKU, a genetic disorder affecting approximately 50,000 diagnosed patients in the developed world, is caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH). PAH is required for the metabolism of phenylalanine (Phe), an essential amino acid found in all protein-containing foods. If the active enzyme is not present in sufficient quantities, Phe accumulates to abnormally high levels in the blood and brain, resulting in a variety of complications including severe mental retardation and brain damage, mental illness, seizures and tremors, and cognitive problems. As a result of global newborn screening efforts implemented in the 1960s and early 1970s, virtually all PKU patients in developed countries are diagnosed at birth.

About tetrahydrobiopterin (BH4) deficiency

BH4 deficiency is a very rare inborn error of metabolism, and is estimated to account for 1-2 % of cases of HPA. BH4 deficiency is an autosomal recessive genetic condition and can result from deficiencies of any of the five different enzymes involved in BH4 synthesis and regeneration. BH4 is a necessary co-factor for PAH. Therefore, BH4 deficiency impairs PAH activity leading to a biochemical situation similar to PKU, with HPA resulting from deficient conversion of Phe to tyrosine. In addition, since BH4 is also a necessary co-factor for both tyrosine hydroxylase and tryptophan hydroxylase, BH4 deficiency causes deficiencies in the downstream neurotransmitter products of these amino acids including catecholamines and serotonin. Dietary limitation of whole protein or Phe intake is often not necessary with BH4 treatment. However, since BH4 does not cross the blood brain barrier, concomitant therapy with neurotransmitter precursors, i. e. levodopa and 5-hydroxytryptophan, may be necessary to boost central nervous system substrate levels for catecholamine and serotonin synthesis, respectively.

About Kuvan^®

Developed by Merck Serono and BioMarin Pharmaceutical Inc. (Nasdaq and SWX: BMRN), Kuvan^® (sapropterin dihydrochloride), is an oral therapeutic and the first treatment indicated in Europe for the treatment of hyperphenylalaninemia (HPA) due to phenylketonuria (PKU) in patients over the age of 4, or due to tetrahydrobiopterin (BH4) deficiency. In the US, Kuvan^® is indicated for the treatment of HPA due to PKU without age restriction. Kuvan^® is to be used in conjunction with a Phe-restricted diet.

Kuvan^® 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 show that Kuvan produces significant reductions in blood Phe levels in the subset of patients who are BH4-responsive.

Most common side effects reported with the use of Kuvan^® include headache, runny nose, diarrhea, vomiting, sore throat, cough, abdominal pain, stuffy nose and low levels of phenylalanine in the blood.

Kuvan^® is approved in 32 countries, including member states of the European Union and the USA. Under the terms of the agreement with BioMarin, Merck Serono has exclusive rights to market Kuvan^® in all territories outside the USA, Canada and Japan.

About Merck Serono

Merck Serono is the biopharmaceutical division of Merck KGaA, Darmstadt, Germany, a global pharmaceutical and chemical company. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets prescription medicines of both chemical and biological origin in specialist indications. In the United States and Canada, EMD Serono operates as a separately incorporated affiliate of Merck Serono.

Merck Serono has leading brands serving patients with cancer (Erbitux®, cetuximab), multiple sclerosis (Rebif®, interferon beta-1a), infertility (Gonal-f®, follitropin alfa), endocrine and metabolic disorders (Saizen® and Serostim®, somatropin), (Kuvan®, sapropterin dihydrochloride), (Egrifta™, tesamorelin), as well as cardiometabolic diseases (Glucophage®, metformin), (Concor®, bisoprolol), (Euthyrox®, levothyroxine). Not all products are available in all markets.

With an annual R&D expenditure of over € 1bn, Merck Serono is committed to growing its business in specialist-focused therapeutic areas including neurodegenerative diseases, oncology, fertility and endocrinology, as well as new areas potentially arising out of research and development in rheumatology.

About Merck

Merck is a global pharmaceutical and chemical company with total revenues of € 9.3 billion in 2010, a history that began in 1668, and a future shaped by more than 40,000 employees in 67 countries. Its success is characterized by innovations from entrepreneurial employees. Merck's operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.

For more information, please visit http://www.merckserono.com or http://www.merck.de