BioMarin Pharmaceutical Inc announced positive results from a pilot clinical study of 6R-BH4 in 20 patients with phenylketonuria (PKU). 6R-BH4 is the active agent in Phenoptin, an investigational small molecule therapeutic for the treatment of PKU. The company has received orphan drug designation for Phenoptin in both the United States and European Union, a company release said.

"The results from this study provide us with valuable new insights that will help us design future clinical trials of Phenoptin in PKU, including a trial we expect to start later this year," said Stuart Swiedler, vice president of Clinical Affairs at BioMarin. He added, "Data from this pilot study indicate that 6R-BH4 can lower blood Phe levels and may allow many PKU patients to significantly relax or eliminate their severely restrictive protein-free diet."

The open-label study enrolled 20 PKU patients at two clinical sites located in the United States. Patients were given 10 mg/kg oral doses of 6R-BH4 daily for seven days. Blood phenylalanine (Phe) levels were measured before treatment and on the first, third and seventh day of 6R-BH4 treatment. Following completion of this first dosing regimen, patients did not take 6R-BH4 for one week. The experiment was then repeated at a dose of 20 mg/kg per day for seven days. Patients were not on a strict low Phe diet prior to or during the study.

The average Phe reduction for all 20 PKU patients in the study after seven days of treatment with 6R-BH4 was 24 per cent at 10 mg/kg and 36 per cent for 20 mg/kg. The study demonstrated that nine out of 20 patients (45 per cent) responded with a 30 per cent or greater reduction in blood Phe levels after receiving a daily dose of 10 mg/kg of 6R-BH4 for seven days.

The number of patients that responded with a 30 per cent or greater reduction in blood Phe levels increased to 12 out of 20 patients (61 per cent) with daily doses of 20 mg/kg of 6R-BH4 for seven days.

The average blood Phe reduction in responders at the 10 mg/kg dose was 50 per cent, while the average reduction in responders at the 20 mg/kg dose was 64 per cent. A responder was defined as a patient who had a 30 per cent or greater drop in blood Phe after the seventh day of 6R-BH4 treatments.

In study, the blood Phe levels in responders rose sharply seven days after
discontinuing treatment with 6R-BH4, providing additional evidence that oral 6R-BH4 can reduce blood Phe levels.

Richard Koch, professor Emeritus of Clinical Pediatrics, University of Southern California School of Medicine, Los Angeles and investigator in the study commented, "While newborn PKU screening and the availability of a medical food diet have helped people with PKU prevent the most serious symptoms of PKU, there is still a significant need for an alternative to diet restriction."

Dr. Koch continued, "Most patients become non-compliant with this highly restricted diet in adolescence, despite the known poor neurological outcomes. Results from this study suggest that a large percentage of people with PKU could potentially benefit from Phenoptin; those with the milder forms of PKU may be able to abandon the low Phe diet completely and those with the more severe form of PKU may also benefit but to a lesser degree.

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.