The Phase I study will assess the safety and pharmacokinetics of single injections of PEG-PAL (poly ethylene glycol-phenylalanine ammonia lyase) in approximately 35 phenylketonuria (PKU) patients in a series of escalating dose cohorts. The patients in the Phase I study will be offered continuation into a Phase II study that will evaluate the safety and efficacy of weekly injections for eight weeks followed by a dose titration period.
The Phase I study will assess the safety and pharmacokinetics of single injections of PEG-PAL in approximately 35 PKU patients in a series of escalating dose cohorts. The patients in the Phase I study will be offered continuation into a Phase II study that will evaluate the safety and efficacy of weekly injections for eight weeks followed by a dose titration period.
Preclinical data has demonstrated that PEG-PAL administered subcutaneously once weekly to PKU mice resulted in a sustained decrease in blood phenylalanine (Phe) levels in a twelve week study and has also shown potent Phe level reductions in primates.
PKU is a genetic disorder caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH), which 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.