BioMarin Pharmaceutical Inc. announced that it has initiated its clinical programme for the treatment of phenylketonuria (PKU), originally projected to start at the end of March. PKU, an enzyme deficiency disorder that can cause mental retardation and brain damage, affects at least 50,000 diagnosed people in the developed world. This first pilot trial, which is expected to be completed in the second quarter of 2004, will evaluate PKU patient responsiveness to the enzyme cofactor 6R-BH4. The aim of this study is to define the 6R-BH4 screening method that will be used to identify the population of PKU patients that will most likely respond in future clinical trials to Phenoptin, BioMarin's proprietary form of 6R-BH4.

"The study represents an important first step towards improving patient care in PKU, a relatively common genetic disease that requires lifelong management," stated Richard Koch, professor emeritus of Clinical Pediatrics at the University of Southern California School of Medicine. "Phenoptin has the potential to reduce high, neurotoxic phenylalanine levels, thereby addressing the underlying cause of both the acute and chronic symptoms of PKU. Such a pharmacologic approach would be more desirable than the conventional method that relies on a highly restricted medical food diet."

This study will build upon the large body of positive clinical data using 6R-BH4 in PKU patients and could accelerate clinical development of Phenoptin. BioMarin expects to start at least one additional clinical trial in PKU by the end of the year.

Fredric Price, CEO of BioMarin, commented, "Phenoptin is an excellent strategic fit for BioMarin, as it meets our primary product development criteria: its addresses a significant medical need, it offers the opportunity to be first to market, and the underlying biology and mechanism of action are well understood." Price also noted, "Phenoptin leverages our experience in designing and conducting clinical trials in the genetic diseases arena and is aligned with our corporate goal of building a commercial enterprise with a focus on genetics and pediatrics."

The study will evaluate the effect of five different 6R-BH4 regimens on blood phenylalanine (Phe) levels. The open-label study will enroll 20 PKU patients over eight years of age and will be conducted at two sites.

PKU, a genetic disorder affecting at least 50,000 diagnosed patients under the age of 40 in the developed world, is caused by a deficiency of the enzyme, phenylalanine hydroxylase (PAH). PAH is required for the metabolism of (Phe), 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 global newborn screening efforts implemented in the 1960s and early 1970s, virtually all PKU patients 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 find difficult to maintain.