BioMarin Reports Positive Phase 3 Results for PALYNZIQ in Adolescent PKU Patients
Key Insights
BioMarin's Phase 3 PEGASUS trial demonstrated a 49.7% reduction in blood phenylalanine levels in adolescents aged 12-17 with PKU (search) treated with PALYNZIQ compared to diet alone.
The study showed 45.2% of PALYNZIQ-treated adolescents achieved ≥50% reductions in phenylalanine levels after 72 weeks, versus only 5.9% in the diet-only group.
BioMarin plans to submit regulatory applications for adolescent label expansion in the second half of 2025, with approval anticipated by 2026.
BioMarin Pharmaceutical Inc. announced positive results from its Phase 3 PEGASUS trial evaluating PALYNZIQ (pegvaliase-pqpz) in adolescents with phenylketonuria (search) (PKU (search)), demonstrating significant blood phenylalanine reduction compared to diet alone. The data were presented at the 15th International Congress of Inborn Errors of Metabolism in Kyoto, Japan.
Trial Design and Patient Population
The PEGASUS study enrolled 55 adolescents aged 12-17 with PKU (search), randomized to receive PALYNZIQ (n=36) or diet alone (n=19). At baseline, participants had a mean age of 14.3 years and mean blood phenylalanine levels of 1026.4 µmol/L. Nearly half (49.1%) of participants had blood phenylalanine levels above 1000 µmol/L at study entry.
Primary Efficacy Results
After 72 weeks of treatment, PALYNZIQ demonstrated statistically significant blood phenylalanine lowering compared to diet alone. The treatment group achieved a 49.7% decrease in mean blood phenylalanine levels. Notably, 45.2% of participants in the PALYNZIQ arm (n=14) achieved reductions in blood phenylalanine concentrations of 50% or more from baseline, compared to just 5.9% in the diet-only group.
"These data from the PEGASUS study underscore the impact PALYNZIQ can have in enabling adolescents to experience more freedom from the burden of their condition, particularly during this pivotal period of transition to adulthood," said Greg Friberg, M.D., Executive Vice President and Chief Research & Development Officer at BioMarin.
Safety Profile
The safety profile observed in adolescents was consistent with the known profile in adults, with manageable adverse events. Serious adverse events occurred in 5.6% of participants, specifically anaphylaxis leading to study discontinuation. The ongoing extension phase of the PEGASUS trial will continue to evaluate long-term results of PALYNZIQ treatment for adolescents.
Regulatory Timeline and Market Impact
BioMarin is on track with its planned submission of the PEGASUS study data to global health authorities during the second half of 2025 to expand the approved indication for PALYNZIQ to include treatment of adolescents. The company anticipates regulatory approval by 2026.
PALYNZIQ currently holds 41.94% of the PKU (search) treatment market, with a 10.69% compound annual growth rate projected through 2030. The global PKU treatment market is projected to grow at a 9.38% CAGR, reaching $1.44 billion by 2030. Analysts estimate that label expansion could add $100-150 million in annual revenue for BioMarin, with potential peak sales reaching $800-900 million annually.
Current Treatment Landscape
PALYNZIQ is currently the first and only enzyme substitution therapy approved to reduce blood phenylalanine concentrations for adults in the U.S., for people 16 and older in the EU, Canada and Brazil, and for people 15 and older in Japan with PKU (search) who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management.
The drug substitutes the deficient phenylalanine hydroxylase (search) (PAH) enzyme in PKU (search) with a PEGylated version of the enzyme phenylalanine ammonia lyase (search) to break down phenylalanine. PKU affects approximately 70,000 people in the regions where BioMarin operates, with epidemiological data suggesting that nearly 60% of PKU cases in major markets occur in patients aged 14 or younger.
Clinical Significance
PKU (search) is a genetic condition requiring lifelong management through severe phenylalanine-restricted diets. Poor control of phenylalanine in adolescence and adulthood is associated with a range of neurocognitive disabilities with significant functional impact. The PEGASUS results suggest PALYNZIQ could reduce the burden of lifelong dietary restrictions, a major challenge for adolescent PKU patients during this critical developmental period.