At a Glance
- FDA approves BioMarin’s PALYNZIQ for PKU adolescents aged 12+, expanding enzyme therapy access beyond adults.
- Phase 3 PEGASUS trial shows significant Phe reduction (-473 μmol/L) vs diet alone at Week 72 in uncontrolled teens.
- 44% reached guideline Phe levels; many normalized diet, boosting protein intake and cutting medical foods.
- Anaphylaxis risk managed via REMS; hailed by experts for easing adolescent PKU management challenges.
Written By: Pharmacally Medical News Desk
BioMarin Pharmaceutical Inc. announced FDA approval of its supplemental Biologics License Application for PALYNZIQ (pegvaliase-pqpz) to treat Pediatric patients aged 12 and older with phenylketonuria (PKU). This expands access to the only approved enzyme substitution therapy that reduces blood phenylalanine (Phe) levels independently of genotype, allowing an unrestricted diet.
Greg Friberg, EVP and Chief Research & Development Officer, BioMarin said “We are proud to build on this legacy by expanding PALYNZIQ’s approval to adolescents as young as age 12, which will allow even more people with PKU the prospect of achieving substantially lower Phe levels.”
PEGASUS Study Results
The approval stems from the Phase 3 PEGASUS trial, a multi-center, open-label study in adolescents aged 12-17 with uncontrolled Phe >600 µmol/L despite existing management. Patients were randomized to PALYNZIQ or diet alone.
At Week 72, PALYNZIQ reduced mean blood Phe by 473 µmol/L (from 1025 baseline) versus 19 µmol/L in the diet arm, yielding a treatment difference of -409 µmol/L (95% CI: -579 to -240).
As presented at the 15th International Congress of Inborn Errors of Metabolism, Part 1, 44.4% reached guideline-recommended Phe levels; 75% of responders were below 120 µmol/L with 94% average reduction. Some achieved hypophenylalaninemia (<30 µmol/L), increasing intact protein intake by 318% and reducing medical food use.
Safety Profile
Common adverse reactions (≥20%) in adolescents included injection site reactions, arthralgia, headache, pyrexia, hypersensitivity, dizziness, nausea, vomiting, fatigue, and extremity pain. Most occurred during induction/titration and lessened in maintenance, aligning with adult data.
Dr. Stephanie Sacharow, Director, Dr. Harvey Levy Program for PKU and Related Conditions, Boston Children’s Hospital said Adolescence challenges PKU patients with independence and academic demands, making restrictive diets unsustainable and risking neurocognitive harm. PALYNZIQ, the only genotype-independent therapy, normalizes Phe on an unrestricted diet, with best adherence in family-supported teens under 18.
Catherine Warren, Executive Director, National PKU Alliance said PALYNZIQ’s FDA approval offers adolescents 12+ a key tool for better Phe management amid major life changes, setting teens up for success into adulthood.
About PALYNZIQ
PALYNZIQ replaces the missing phenylalanine hydroxylase (PAH) enzyme in PKU patients with a PEGylated form of phenylalanine ammonia lyase, which effectively degrades excess Phe. It follows a tolerability-optimized dosing schedule, though its safety profile features mainly immune-related reactions including potential anaphylaxis managed successfully in trials through stringent protocols.
Due to this anaphylaxis risk, PALYNZIQ is dispensed exclusively via the PALYNZIQ REMS restricted program; Please refer full prescribing information for details including the Boxed Warning, precaution and warnings and adverse reactions.
PKU Disease Overview
PKU is a genetic disorder caused by phenylalanine hydroxylase (PAH) deficiency, affecting about 70,000 people in BioMarin’s operational regions. Without sufficient PAH enzyme, Phe from protein-rich foods accumulates, causing brain toxicity that leads to intellectual disability, seizures, and behavioural issues if unmanaged.
Newborn screening enables early diagnosis and lifelong management via a strict Phe-restricted diet with medical foods. However, adherence challenges in adolescence often result in poor Phe control and neurocognitive deficits.
Reference
U.S. Food and Drug Administration Approves BioMarin’s PALYNZIQ® (pegvaliase-pqpz) for Adolescents 12 Years of Age and Older with Phenylketonuria (PKU), 27 February 2026, BioMarin Pharmaceutical Inc. – U.S. Food and Drug Administration Approves BioMarin’s PALYNZIQ® (pegvaliase-pqpz) for Adolescents 12 Years of Age and Older with Phenylketonuria (PKU)