FDA approves PALYNZIQ for adolescents with phenylketonuria

Pegvaliase-pqpz (PALYNZIQ; BioMarin Pharmaceutical Inc.) has received FDA approval for managing phenylketonuria (PKU) in pediatric patients aged 12 years and older, according to BioMarin Pharmaceutical.¹

This approval is supported by positive results from the phase 3 PEGASUS trial, which assessed safety and efficacy outcomes in adolescents aged 12 to under 18 years with blood phenylalanine (Phe) concentrations greater than 600 µmol/L. When compared to diet alone, pegvaliase-pqpz showed a significantly greater reduction in mean blood Phe levels by week 52.

“The ultra-restrictive diet required for PKU management may become unsustainable, and poor blood Phe control leads to adverse neurocognitive outcomes. PALYNZIQ is the only genotype-independent medication which may bring Phe into the normal range while allowing an unrestricted diet," said Stephanie Sacharow, MD, director at Boston Children’s Hospital.

Efficacy and protein intake improvements

There were 36 patients included in the pegvaliase-pqpz group and 19 in the diet only group. Mean changes in blood Phe levels at week 72 in these groups were -473 and -19, respectively, with an overall treatment difference of -409 reported.

These results highlighted 44.4% of patients reaching levels below guideline recommendations, 75% of whom reached levels below 20 µmol/L. The average Phe reduction in these patients was 828 µmol/L.

Additionally, there were 9 patients with blood Phe levels below 30 µmol/L, defined as hypophenylalaninemia. These patients were able to increase their protein intake by 318.1% and reduce their medical food protein intake by 55.16% from baseline.

Adverse reactions and traditional PKU management

Common adverse reactions appearing in 20% or more of the pegvaliase-pqpz group included headache, hyperensensitivity reactions, pyrexia, arthralgia, nausea, dizziness, vomiting, injection site reactions, fatigue, and pain in extremity. Most reactions occurred in the induction/titration phase and were less frequent in the maintenance phase.

PKU is defined as a condition where there is not a sufficient amount of the phenylalanine hydroxylase enzyme, which is necessary for metabolism of Phe. This leads to abnormally high levels of Phe that become toxic to the brain, causing complications such as severe intellectual disability, tremors, seizures, psychiatric symptoms, and behavioral problems.

Traditionally, a severe Phe-restricted diet is used to manage PKU, with supplementation given through low-protein modified foods and Phe-free medical foods. However, most patients struggle to adhere to the strict diet necessary to adequately control blood Phe levels.

Risks and benefits of pegvaliase-pqpz

Pegvaliase-pqpz breaks down Phe with a PEGylated version of the enzyme phenylalanine ammonia lyase, significantly improving Phe levels. The dosing regimen is designed to facilitate tolerability, and the safety profile primarily includes immune-mediated responses such as anaphylaxis.

Considering the risk of anaphylaxis, experts recommend the initial dose is performed under the supervision of a health care provider capable of managing anaphylaxis. Patients should be observed for at least 1 hour following injection.

Epinephrine should also be prescribed to all patients treated with pegvaliase-pqpz, with patients and any adult observers being instructed on its appropriate use before the first dose. Additionally, patients should be instructed to seek immediate medical care upon its use.

Expanding treatment options for adolescents

“In my clinic we have found that PALYNZIQ treatment adherence is even more successful in teens under age 18, while they are living at home with family support, and this approval allows us to extend this therapeutic option to adolescents who may benefit most,” said Sacharow.

This marks a new option for pediatrics treatment of PKU. Last year, the FDA also approved PTC Therapeutics' sepiapterin (Sephience) to treat the condition in adult and pediatric patients.² However, this was designed to be used in combination with a Phe-restricted diet, allowing for an increase in protein.

"[Sepiapterin and a Phe-restricted diet will go] hand in hand. The approach has always centered on diet, with pharmacologic management as an adjunct to hopefully help liberalize diet," said Timothy Tramontana, MD, medical and biochemical geneticist at Cleveland Clinic Foundation.

References

1. US Food and Drug Administration approves BioMarin’s PALYNZIQ® (pegvaliase-pqpz) for adolescents 12 years of age and older with phenylketonuria (PKU). BioMarin. February 27, 2026. Accessed March 2, 2026. https://www.biomarin.com/news/press-releases/u-s-food-and-drug-administration-approves-biomarins-palynziq-pegvaliase-pqpz-for-adolescents-12-years-of-age-and-older-with-phenylketonuria-pku/
2. Fitch J. FDA approves sepiapterin to treat phenylketonuria in adult, pediatric patients. Contemporary Pediatrics. July 29, 2025. Accessed March 2, 2026. https://www.contemporarypediatrics.com/view/fda-approves-sepiapterin-to-treat-phenylketonuria-in-adult-pediatric-patients