BioMarin Pharmaceutical Inc., develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions, has started phase III programme for PEG-PAL (PEGylated recombinant Phenylalanine Ammonia Lyase) for the treatment of phenylketonuria (PKU).

"In the phase II trial, PEG-PAL was shown to dramatically reduce blood Phe levels, and we are hopeful that we will achieve the same outcome with the phase III programme," stated Hank Fuchs, MD, chief medical officer of BioMarin. "Adult patients with PKU and patients on the severe end of the disease spectrum still represent a very high unmet medical need. With PEG-PAL, it may be possible to provide a treatment benefit to this population."

The phase III study (165-301) is an open-label, multi-centre study to assess the safety and tolerability of an induction, titration and maintenance dose regimen of PEG-PAL self-administered by approximately 90 naïve adult PKU subjects. The primary objective of the 165-301 study is to characterize the safety and tolerability of PEG-PAL during induction, titration, and maintenance dosing. The secondary objective of the study is to evaluate blood Phe levels during induction, titration, and maintenance dosing.

After completion of the open label 165-301 study, subjects are expected to enroll in 165-302, a phase III double-blind, placebo-controlled, randomized discontinuation study to evaluate the efficacy and safety of PEG-PAL self-administered by adults with PKU. The study will also enroll approximately 60 subjects from the phase II programme who are currently being treated with PEG-PAL. The primary objective of the 165-302 study is to evaluate blood Phe levels. The secondary objective of this study is to evaluate changes in neuropsychiatric assessments as measured by the Inattentive portion of the Attention Deficit and Hyperactivity Disorder Rating Scale (ADHD-RS) and the Profile of Mood States (POMS). These will be administered at baseline, four and eight weeks.

PKU, a genetic disorder is caused by a deficiency of the enzyme phenylalanine hydroxylase. 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. Currently, PKU can only be managed by a Phe-restricted diet, which is supplemented by nutritional replacement products, like formulas and specially-manufactured foods; however, the strict diet is difficult for most patients to adhere to the extent needed for achieving adequate control of blood Phe levels.

BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions.