Novel Enzyme Therapy Approved for Genetic Disease Phenylketonuria | FDA

The US FDA has approved pegvaliase (Palynziq®, BioMarin Inc) for the treatment of phenylketonurea (PKU) uncontrolled by conventional therapy.


  • Pegylated recombinant bacterial Anabaena variabilis phenylalanine ammonia lyase
  • Subcutanous daily injection, 5-60 mg
  • 51.1% decrease in blood Phe levels after 12 months of therapy
  • Half of patients on treatment achieve blood Phe level < 120 µmol/L, the upper limit of normal range, within 2 years
  • Adverse events (common): arthralgia (70.5%), injection-site reaction (62.1%), headache (47.1%)
  • Adverse events (severe): anaphylaxis (4.6%)
  • Current treatment: dietary phenylalanine restriction, sapropterin in THB-responsive PKU


  • 2 Phase III clinical trials (PRISM-1, PRISM-2)
  • PRISM-2: randomized placebo-controlled trial, double-blind
  • 261 adult patients w/ PKU and blood Phe > 600 µmol/L
  • 33% discontinued pegvaliase due to adverse events
  • Funded by BioMarin Inc.

What is PKU?

PKU affects 7-10 per 100,000 people in the United States and is characterized by toxic accumulation of the amino acid phenylalanine, leading to extensive intellectual, neurodevelopmental and psychiatric disabilities.  PKU is most often caused by deficient or malfunctioning phenylalanine hydroxylase (PAH) enzyme.  PAH catalyzes the conversion of phenylalanine to tyrosine, a key step in the biosynthesis of the neurotransmitter dopamine.  Less common forms of PKU, caused by deficiency of the PAH cofactor THB, may respond to sapropterin (Kuvan®), a synthetic form of THB.  Restriction of dietary phenylalanine intake starting in infancy is critical in order to avoid irreversible neurological damage.

What is pegvaliase?

Pegvaliase is a recombinant bacterially derived enzyme that degrades the amino acid phenylalanine, reducing phenylalanine burden and lowering the risk of neurotoxicity in patients with PKU.  It is administered via once-daily subcutaneous injection.

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