FDA approved a supplemental Biologics License Application (BLA) for BioMarin Pharmaceutical Inc.’s Palynziq (pegvaliase-pqpz) to include pediatric patients 12 years of age and older with phenylketonuria (PKU).

The approval expands access to the only enzyme substitution therapy approved to reduce blood phenylalanine (Phe) concentrations in people with the condition.¹

“Today’s FDA approval for Palynziq is an important step forward for the PKU community, providing a new option for adolescents ages 12 and older that has the potential to improve daily PKU management,” said Catherine Warren, executive director of the national PKU Alliance.

Palynziq substitutes the deficient phenylalanine hydroxylase enzyme in PKU with a PEGylated version of phenylalanine ammonia lyase to break down Phe.¹ Due to the risk of anaphylaxis, the therapy is available only through a Risk Evaluation and Mitigation Strategy program.¹

What is Palynziq’s approval based on?

The approval is based on results from Pegasus, a Phase III multi-center, open-label randomized controlled study evaluating the safety and efficacy of Palynziq compared with diet alone in adolescents aged 12 to younger than 18 with PKU who had uncontrolled blood Phe concentrations greater than 600 µmol/L on existing management.²

Participants receiving Palynziq showed a significant mean reduction in blood Phe levels at Week 72 compared with those in the diet-only arm.²

What are the results of the Pegasus phase III trial?

At baseline, mean blood Phe levels were 1025 µmol/L in the Palynziq group and 1029 µmol/L in the diet-only group. By Week 72, mean Phe levels were 567 µmol/L in the Palynziq arm compared with 973 µmol/L in the diet-only arm. The mean change from baseline at Week 72 was -473 µmol/L in the Palynziq group versus -19 µmol/L in the diet-only group, with a treatment difference of -409 µmol/L.

“Adolescence is a period of increasing independence and academic demands and represents a particularly challenging time for individuals with PKU,” said Dr. Stephanie Sacharow, director of the Dr. Harvey Levy Program for PKU and Related Conditions at Boston Children’s Hospital. “Palynziq is the only genotype-independent medication which may bring Phe into the normal range while allowing an unrestricted diet.” She added that in her clinic, treatment adherence has been more successful in teens under 18 who are living at home with family support.

Additional data presented at the 15th International Congress of Inborn Errors of Metabolism showed that by the end of Part 1 of the study, 44.4% of participants reached Phe levels below guideline recommendations.²

Of those individuals, 75% were below 120 µmol/L, with an average reduction of 828 µmol/L, representing a 94% decrease from baseline. Nine participants with blood Phe levels below 30 µmol/L were able to increase intact protein intake by 318.1% from baseline and reduce medical food protein intake by 55.16%, with six discontinuing medical food completely.

What were the adverse reactions?

The most common adverse reactions in adolescents, occurring in at least 20% of patients, included injection site reactions, arthralgia, headache, pyrexia, hypersensitivity reactions, dizziness, nausea, vomiting, fatigue and pain in extremity.¹ As in previous clinical studies, most reactions occurred during the induction and titration phase and decreased in frequency during maintenance.

“Over the past two decades, BioMarin has been working hand-in-hand with the medical and advocacy communities to improve the lives of people living with PKU,” said Greg Friberg, executive vice president and chief research & development officer at BioMarin. “We are proud to build on this legacy by expanding Palynziq’s approval to adolescents as young as age 12.”

What are the next steps for Palynziq?

BioMarin is also seeking approval from the European Medicines Agency to expand treatment with Palynziq to adolescents as young as 12 in the European Union.¹

Sources

1. U.S. Food and Drug Administration Approves BioMarin's PALYNZIQ (pegvaliase-pqpz) for Adolescents 12 Years of Age and Older with Phenylketonuria (PKU) BioMarin Pharmaceuticals Inc. February 27, 2026 https://www.prnewswire.com/news-releases/us-food-and-drug-administration-approves-biomarins-palynziq-pegvaliase-pqpz-for-adolescents-12-years-of-age-and-older-with-phenylketonuria-pku-302700090.html
2. BioMarin Announces Positive Pivotal Data for PALYNZIQ (pegvaliase-pqpz) in Adolescents with Phenylketonuria BioMarin Pharmaceuticals Inc. April 2, 2025 https://www.prnewswire.com/news-releases/biomarin-announces-positive-pivotal-data-for-palynziq-pegvaliase-pqpz-in-adolescents-with-phenylketonuria-302417762.html