PEG-PAL
PEG-PAL Uses, Dosage, Side Effects, Food Interaction and all others data.
PEG-PAL is a recombinant phenylalanine ammonia lyase (PAL) enzyme derived from Anabaena variabilis that converts phenylalanine to ammonia and trans-cinnamic acid . Both the U.S. Food and Drug Administration and European Medicines Agency approved pegvaliase-pqpz in May 2018 for the treatment of adult patients with phenylketonuria (PKU). Phenylketonuria is a rare autosomal recessive disorder that is characterized by deficiency of the enzyme phenylalanine hydroxylase (PAH) and affects about 1 in 10,000 to 15,000 people in the United States . PAH deficiency and inability to break down an amino acid phenylalanine (Phe) leads to elevated blood phenylalanine concentrations and accumulation of neurotoxic Phe in the brain, causing chronic intellectual, neurodevelopmental and psychiatric disabilities if untreated . Individuals with PKU also need to be under a strictly restricted diet as Phe is present in foods and products with high-intensity sweeteners . The primary goal of lifelong treatment of PKU, as recommended by the American College of Medical Genetics and Genomics (ACMG) guidelines, is to maintain blood Phe concentration in the range of 120 µmol/L to 3690 µmol/L . PEG-PAL-pqpz, or PEGylated pegvaliase, is used as a novel enzyme substitution therapy and is marketed as Palynziq for subcutanoues injection. It is advantageous over currently available management therapies for PKU, such as Sapropterin, that are ineffective to many patients due to long-term adherence issues or inadequate Phe-lowering effects . The presence of a PEG moiety in pegvaliase-pqpz allows a reduced immune response and improved pharmacodynamic stability .
In a phase 3 clinical trial of adult patients with phenylketonuria and blood phenylalanine concentrations greater than 600 µmol/L on existing management therapies, subcutaneous administration of pegvaliase resulted in significantly reduced blood phenylalanine concentrations in most patients compared to their pre-treatment baseline levels within 24 months in addition to improved neuropsychiatric symptoms .
| Trade Name | PEG-PAL |
| Availability | Prescription only |
| Generic | Pegvaliase |
| Pegvaliase Other Names | PEG-PAL, Pegvaliase, pegvaliase-pqpz, Phenylase, rAvPAL-PEG |
| Related Drugs | Kuvan, sapropterin, Palynziq |
| Type | |
| Formula | C15H30N2O5 |
| Weight | Average: 318.414 Monoisotopic: 318.215472074 |
| Protein binding | No protein binding has been reported. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
PEG-PAL is an enzyme used to treat phenylketonuria in patients with phenylalanine levels that are too high on current treatment.
PEG-PAL is indicated for the management of phenylketonuria (PKU) in adult patients who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management.
PEG-PAL is also used to associated treatment for these conditions: Uncontrolled phenylketonuria
How PEG-PAL works
PEG-PAL is a phenylalanine ammonia lyase (PAL) enzyme that temporarily restores the levels of deficient enzyme and reduces blood phenylalanine concentrations by converting phenylalanine to ammonia and trans-cinnamic acid . Formed conversion products are metabolized in the liver and later excreted in the urine .
Toxicity
No LD50 value has been reported for pegvaliase. A subcutaneous dose of 20 mg/kg/day of pegvaliase-pqpz produced impaired fertility in female rats leading to decreases in corpora lutea, implantations, and litter size, in association with toxic effects including decreased weight, ovarian weight, and food consumption . The carcinogenic and genototoxic potential have not been studied.
Food Interaction
No interactions found.Volume of Distribution
The mean ± SD (range) apparent volume of distribution at steady state was 26.4 ± 64.8 (1.8 to 241) L and 22.2 ± 19.7 (3.1 to 49.5) L after once-daily subcutaneous administration of 20 mg and 40 mg pegvaliase, respectively .
Elimination Route
At steady state during maintenance treatment with pegvaliase 20 mg and 40 mg subcutaneously once daily, the mean ± SD (range) peak plasma concentration (Cmax) was 14.0 ± 16.3 (0.26 to 68.5) mg/L and 16.7 ± 19.5 (0.24 to 63.8) mg/L, respectively . The time to reach Cmax (Tmax) was approximately 8 hours .
Half Life
Following once-daily subcutaneous administration of 20 mg and 40 mg pegvaliase, the mean ± SD (range) half-life at steady state was 47 ± 42 (14 to 132) hours and 60 ± 45 (14 to 127) hours, respectively .
Clearance
At steady state following once-daily subcutaneous administration of 20 mg and 40 mg pegvaliase, the mean ± SD (range) apparent clearance was 0.39 ± 0.87 L/h and 1.25 ± 2.46 L/h, respectively .
Elimination Route
Human elimination pathway of pegvaliase has not been studied.
Innovators Monograph
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