BioMarin Pharmaceutical (Nasdaq and SWX: BMRN) has submitted a NDA (New Drug Application) to the FDA for Kuvan (sapropterin dihydrochloride), an investigational oral small molecule for the treatment of patients with PKU (phenylketonuria) being developed in partnership with Merck Serono. Merck Serono expects to file a MAA for Kuvan with the EMEA in the third quarter of 2007.

"This NDA filing represents a significant milestone in our PKU program and our efforts to bring the first treatment option to PKU patients," said Jean-Jacques Bienaime, Chief Executive Officer of BioMarin. "The NDA filing contains data evaluating Kuvan in approximately 650 human subjects in six clinical studies and represents BioMarin's largest and most comprehensive filing to date. The company is now gearing up for the U.S. launch of Kuvan in late 2007 or early 2008."

About Kuvan
Kuvan is an investigational oral small molecule therapeutic for the treatment of PKU. The active ingredient in Kuvan, sapropterin dihydrochloride, is the synthetic form of 6R-BH4 (tetrahydrobiopterin), a naturally occurring enzyme cofactor that works in conjunction with phenylalanine hydroxylase (PAH) to metabolize Phe. Clinical data suggests that Kuvan produces significant reductions in blood Phe levels in BH4-responsive patients. BioMarin and Merck Serono estimate that Kuvan could be a potential treatment option for approximately 30 per cent to 50 per cent of the estimated 50,000 identified PKU patients in the developed world.

Kuvan has received orphan drug designation from both the FDA and the EMEA. Upon approval, it will receive seven years of market exclusivity in the United States and 10 years in the European Union for this indication. Additionally, the FDA has granted Kuvan Fast Track designation, which is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.

About PKU
PKU, a genetic disorder affecting approximately 50,000 diagnosed patients in the developed world, is caused by a deficiency of the enzyme PAH (phenylalanine hydroxylase). PAH is required for the metabolism of Phe (phenylalanine), an essential amino acid found in most 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 newborn screening efforts implemented in the 1960s and early 1970s, virtually all PKU patients under the age of 40 in developed countries have been diagnosed at birth. The only treatment currently available for PKU patients is a highly restrictive and expensive medical food diet that most patients fail to adhere to the extent needed for achieving adequate control of blood Phe levels.