BioMarin Forges Ahead with Research On PKU Diet Alternatives

From the Spring/Summer 2004 issue of National PKU News

Since the diet for PKU was first used in the 1960's, there have been no major breakthroughs in PKU treament. Even though we have seen many advances in medical formula and low protein food formulation and an increasingly large number of formula and food choices, the diet restrictions are still fundamentally the same. We can be hopeful that one day this will change. A company that has become of key importance in the search for alternatives is BioMarin Pharaceutical Inc. Located in Marin County in northern California, this biopharmaceutical company focuses on developing and commercializing first-to-market biopharmaceuticals to improve the lives of people living with life-threatening diseases or serious medical conditions. They have just established a PKU clinical research program that covers two very different approaches to PKU treatment. Susan Ferris, Corporate Communications Manager at BioMarin, updates us on their current work.

Progress is being made in the effort to develop new treatment options for people with phenylketonuria (PKU). BioMarin's goal is to develop products that will allow people with PKU greater dietary flexibility and add more options for managing their disease. With the help of a PKU advisory board comprised of ten renowned metabolic disease experts, BioMarin Pharmaceutical is developing two approaches to potentially address the full spectrum of PKU: Phenoptin™ (a formulation of the naturally occurring enzyme cofactor, BH4) for mild to moderate PKU, and Phenylase™ (phenyl-alanine ammonia lyase) for classical PKU. Following is a brief overview of these two investigational products and their development status.

Two Approaches: Phenoptin And Phenylase

For people who do not respond to Phenoptin, likely those with the more severe form of PKU and less PAH activity, BioMarin is developing Phenylase. Phenylase is a recombinant form of phenylalanine ammonia lyase, an enzyme that is similar to PAH in metabolizing phe. The company is developing Phenylase as a subcutaneous (just beneath the skin) injectable enzyme substitute therapy. In PKU preclinical mouse models, Phenylase produced a rapid, prolonged dose-dependent reduction in blood phe levels.

Development Status

In February 2004, BioMarin initiated its PKU clinical program, beginning with a pilot trial of tetrahydrobiopterin. The "open-label" trial (a trial in which participants know that they are getting the experimental drug, as opposed to a blinded trial in which participants do not know if they are getting placebo or drug) will enroll 20 PKU patients over 8 years of age. It will evaluate the effect of five different 6R-BH4 screening regimens on blood phe levels. This information will help develop the screening method to identify the population of PKU patients most likely to respond to Phenoptin in future clinical trials. The company expects to complete the pilot trial in the second quarter of 2004. Pending positive regulatory review, we plan to initiate an additional clinical trial of Phenoptin by the end of 2004.

BioMarin plans to conduct other preclinical studies of Phenylase in 2004; if results are positive, we will file an investigational new drug application in 2005. The advisory board will be meeting with BioMarin's PKU project team throughout the year to help advance the development of both Phenoptin and Phenylase.

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