The US Food and Drug Administration (FDA) has approved the supplemental Biologics License Application for Palynziq (pegvaliase-pqpz) to include pediatric patients ages 12 years and older with phenylketonuria (PKU).
Phenylketonuria (PKU) is a genetic metabolic disorder that increases the body’s levels of phenylalanine (Phe) to toxic levels. Phenylalanine is a natural amino acid present in many foods we eat. However, people do not need all the phenylalanine they eat, so the body converts extra
Phe to the relatively harmless amino acid, tyrosine. People with PKU cannot properly break down the extra Phe and convert it to tyrosine, leading to build up of Phe throughout the body, including the brain. Without treatment, children with classic PKU develop permanent intellectual disability. Light skin and hair, seizures, developmental delays, behavioral problems, and psychiatric disorders are also common. In most cases, PKU is caused by mutations in the PAH gene.
Pegvaliase is a PAH enzyme substitution therapy designed to reduce blood Phe concentrations through a PEGylated version of the enzyme phenylalanine ammonia in patients with PKU. Pegvaliase comes with a Boxed Warning for anaphylaxis.
The FDA approval is based on data from the phase 3 multicenter, open-label, randomized, controlled PEGASUS clinical trial. This study evaluated the safety and efficacy of pegvaliase compared to diet alone in patients ages 12 to 18 years with PKU who had uncontrolled blood Phe concentrations greater than 600 µmol/L on existing management.
Patients in the pegvaliase arm showed a significant mean reduction in blood Phe levels from baseline at week 72 compared to those in the diet-only arm. By end of part 1 of the study, 44.4% had reached levels below guideline recommendations. Of those patients, 75% were below 120 µmol/L and their average Phe reduction was 828 µmol/L. Nine patients whose blood Phe levels were below 30 µmol/L were able to increase their intact protein intake by 318.1% from baseline and decrease their intake of medical food protein by 55.16%. A total of six patients discontinued medical food completely.
The most common adverse events in these patients were injection site reactions, arthralgia, headache, pyrexia, hypersensitivity reactions, dizziness, nausea, vomiting, fatigue, and extremity pain. The overall safety profile of pegvaliase observed showed most reactions occurring in the induction/titration phase and decreasing in frequency during the maintenance phase, as aligned with previous clinical studies
For more information, visit the Press Release.
To learn more about PKU and other rare metabolic disorders, visit https://checkrare.com/diseases/metabolic-disorders/
