Results From Investigator-Sponsored Trials Presented at SSIEM Conference

NOVATO, Calif., Sept. 1 /PRNewswire-FirstCall/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) announced today that results from investigator-sponsored studies on Kuvan (sapropterin dihydrochloride) are being presented at the 2010 Annual Symposium of the Society for The Study of Inborn Errors of Metabolism (SSIEM), August 31st-September 3rd in Istanbul, Turkey. Investigators reported that PKU patients taking Kuvan showed improvements in brain functioning, mood and behaviors.

"While these investigator-sponsored studies were conducted in a small number of subjects, the results indicate benefits beyond lowering blood Phe levels, and we hope to document similar neurocognitive improvements in subjects with PKU in our recently initiated Phase 3b Kuvan outcomes study," said Dr. Hank Fuchs, Chief Medical Officer of BioMarin.  "If successful, the data will be submitted in support of a label amendment."

Highlights of Investigator-Sponsored Studies:

Neurocognitive findings in individuals with Phenylketonuria and treatment with sapropterin dihydrochloride (BH4) (White, et al; Washington University, St. Louis): Baseline findings indicate that executive performance is worse for subjects with PKU as compared to non-PKU subjects across a range of executive functions such as inhibitory control, strategic processing and working memory. The results of this exploratory study suggest improvements in executive abilities following treatment with sapropterin.

Brain function in individuals with PKU treated with Kuvan: Evidence from functional magnetic resonance imaging (Christ, et al; University of Missouri-Columbia, USA): At baseline, irregularities in neural activation were observed in subjects with PKU in the prefrontal cortex (PFC) and other brain regions as compared to subjects without PKU. At four weeks, two early-treated PKU participants responded to Kuvan with a >20% reduction in phenylalanine levels and also showed improved activation for a region in the orbitomedial PFC.

Pilot study to evaluate the effects of Kuvan on adult individuals with Phenylketonuria with measurable maladaptive behaviors (Moseley, et al; University of Southern California/Keck School of Medicine): Preliminary six-month data in ten subjects with measurable maladaptive behaviors showed that while there was a small decrease in blood Phe concentrations there was a large decrease in the Phe/Tyr ratio. Additionally, improvements were measured in all negative behaviors, most specifically, irritability and rage.

About Kuvan

Kuvan® (sapropterin dihydrochloride) Tablets are indicated in the United States to reduce blood phenylalanine (Phe) levels in patients with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive phenylketonuria (PKU). Kuvan is to be used in conjunction with a Phe-restricted diet. 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. Kuvan has received orphan drug designation from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA). Kuvan has received seven years of orphan exclusivity in the United States and ten years of market exclusivity in the E.U.

Important Safety Information

Prolonged exposure to elevated blood Phe levels in PKU patients can result in severe neurologic damage. The initiation of KUVAN therapy does not eliminate the need for careful monitoring of blood Phe levels and ongoing dietary management.

Some patients receiving Kuvan can experience significant drops in blood Phe levels. Patients should be monitored closely to ensure that blood Phe levels do not fall too low.

Not all patients with PKU respond to treatment with Kuvan. Response to treatment can only be determined by a therapeutic trial of Kuvan.

Kuvan has not been studied in patients with liver or renal impairment. Patients who have these conditions should be carefully monitored when receiving Kuvan. Caution should be used with the administration of Kuvan to patients who are receiving levodopa and drugs that affect nitric oxide–mediated vasorelaxation or folate metabolism.

The most serious adverse reactions reported during Kuvan administration (regardless of relationship to treatment) were gastritis, spinal cord injury, streptococcal infection, testicular carcinoma, and urinary tract infection. Mild to moderate neutropenia was also noted. The most common adverse reactions were headache, diarrhea, abdominal pain, upper respiratory tract infection, pharyngolaryngeal pain, vomiting, and nausea.

About 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, 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 becomes toxic to the brain, resulting in a variety of complications including severe mental retardation and brain damage, mental illness, seizures, tremors, and limited cognitive ability. 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. To learn more about PKU, please visit www.PKU.com. Information on this website is not incorporated by reference into this press release.

About BioMarin

BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions. The company's product portfolio comprises four approved products and multiple clinical and pre-clinical product candidates. Approved products include Naglazyme® (galsulfase) for mucopolysaccharidosis VI (MPS VI), a product wholly developed and commercialized by BioMarin; Aldurazyme® (laronidase) for mucopolysaccharidosis I (MPS I), a product which BioMarin developed through a 50/50 joint venture with Genzyme Corporation; Kuvan® (sapropterin dihydrochloride) Tablets, for phenylketonuria (PKU), developed in partnership with Merck Serono, a division of Merck KGaA of Darmstadt, Germany; and Firdapse™ (amifampridine phosphate), which has been approved by the European Commission for the treatment of Lambert Eaton Myasthenic Syndrome (LEMS). Other product candidates include GALNS (N-acetylgalactosamine 6-sulfatase), which is currently in Phase I/II clinical development for the treatment of MPS IVA and PEG-PAL (PEGylated recombinant phenylalanine ammonia lyase), which is currently in Phase II clinical development for the treatment of PKU. For additional information, please visit www.BMRN.com. Information on BioMarin's website is not incorporated by reference into this press release.

BioMarin®, Naglazyme® and Kuvan® are registered trademarks of BioMarin Pharmaceutical Inc.

Firdapse™ is a trademark of BioMarin Huxley Ltd.

Aldurazyme® is a registered trademark of BioMarin/Genzyme LLC.

SOURCE BioMarin Pharmaceutical Inc.