Full Press Release Details
New data from Phase 3 PEGASUS study demonstrates a 49.7% decrease in mean blood Phe levels in adolescents aged 12-17 treated with PALYNZIQ
BioMarin's planned submission to global health authorities on track for second half of 2025
SAN RAFAEL, Calif.,Sept. 6, 2025/PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq:BMRN) today announced new data characterizing the efficacy and safety of PALYNZIQ®(pegvaliase-pqpz) for the treatment of adolescents with phenylketonuria (PKU), which were presented at the 15th International Congress of Inborn Errors of Metabolism (ICIEM) inKyoto, Japan,Sept. 2-6, 2025.
The Phase 3 PEGASUS study evaluating the efficacy and safety of PALYNZIQ in adolescents aged 12-17 demonstrated statistically significant blood phenylalanine (Phe) lowering compared to diet alone. The study enrolled 55 adolescents, randomized to receive PALYNZIQ (n=36) or diet alone (n=19). At baseline, the mean age was 14.3 years, mean blood Phe was 1026.4 µmol/L, and nearly half (49.1%) of participants had blood Phe levels above 1000 µmol/L. Notably, after the 72-week primary treatment phase, almost half of participants in the PALYNZIQ arm (n=14; 45.2%) achieved reductions in blood Phe concentrations of 50% or more from baseline, with many reaching guideline-recommended and even normal Phe target levels.
Table 1. Primary and Secondary Efficacy Results After 72 Weeks
PALYNZIQ
(n=31)
Diet only
(n=17)
The safety profile and overall efficacy trends in adolescents were consistent with the known profile of the medicine in adults. The vast majority of adverse events (AEs) in the study were manageable, with 5.6% representing serious AEs (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.
"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," saidGreg Friberg, M.D., Executive Vice President and Chief Research & Development Officer at BioMarin. "BioMarin has been deeply committed to advancing scientific progress for people living with PKU over the past two decades, and we look forward to sharing these results with global regulators with the aim of bringing the unequaled efficacy observed with PALYNZIQ to an even younger group of people."
PALYNZIQ is the first and only enzyme substitution therapy approved to treat adults with PKU. The company is on track with its planned submission of the PEGASUS study data to global health authorities to expand the approved indication for PALYNZIQ to include the treatment of adolescents.
Below are key presentations for BioMarin and PALYNZIQ at ICIEM (all times Japan Standard Time):
Neuropsychiatric Comorbidities in Adults with PKU inSwedenOral #3Wednesday, Sept. 3, 2025,11 a.m.–12:30 p.m.
Safety and Efficacy of Pegvaliase in Adolescents with Phenylketonuria: Primary Results from PEGASUS, a Phase 3, Open-Label Randomized Controlled StudyOral #21Friday, Sept. 5, 2025, 10:15 –11:45 a.m.
Lifetime Monitoring ofPhe Levelsin PKU from Birth to Adulthood in the Swedish Registry for Inherited Metabolic DiseasesPoster #P-593Wednesday, Sept. 3, 2025, 6 –7 p.m.
Work Ability in Adults with PKU inSwedenin 2020Poster #P-594Wednesday, Sept. 3, 2025, 6 –7 p.m.
Neuropsychiatric Comorbidities in Adolescents with PKU inthe United StatesPoster #P-595Wednesday, Sept. 3, 2025, 6 –7 p.m.
PALLADIUM: A Phase 4 Study to Evaluate a Rapid Drug Desensitization Protocol for Adults with Phenylketonuria Experiencing Hypersensitivity Reactions to PegvaliasePoster #P-586Thursday, Sept. 4, 2025, 5:30 –6:30 p.m.
Real-World Safety and Tolerability of Pegvaliase: A Non-Interventional Surveillance Study inJapanPoster #P-584Thursday, Sept. 4, 2025, 5:30 –6:30 p.m.
About PEGASUS
PEGASUS is a Phase 3 multi-center open-label randomized controlled study evaluating the efficacy and safety of PALYNZIQ compared to diet alone in 55 adolescents aged 12-17 with phenylketonuria. The primary endpoints are change in blood Phe concentration and characterization of the safety profile in adolescents. Secondary endpoints include change in total dietary protein intake and pharmacokinetics.
The study is being conducted in two parts: the primary treatment phase ranging from weeks 1-73 (Part 1), and the extension phase (Part 2), which lasts for up to an additional 80 weeks of monitoring for the PALYNZIQ arm and allows for crossover for those in the diet-only arm.
For more information, please visitclinicaltrials.biomarin.com.
About PALYNZIQ
PALYNZIQ substitutes the deficient phenylalanine hydroxylase (PAH) enzyme in PKU with a PEGylated version of the enzyme phenylalanine ammonia lyase to break down Phe. PALYNZIQ is administered using a dosing regimen designed to facilitate tolerability; PALYNZIQ's safety profile consists primarily of immune-mediated responses, which can include anaphylaxis, for which robust risk management measures effective in clinical trials are in place.
PALYNZIQ is approved to reduce blood Phe concentrations for adults in the U.S., for people 16 and older in the EU,CanadaandBrazil, and for people 15 and older inJapanwith PKU who have uncontrolled blood Phe concentrations greater than 600 micromol/L on existing management.
Patient Support Accessing PALYNZIQ
To reach a BioMarin RareConnections®Case Manager, please call, toll-free, 1-866-906-6100 or e-mail[email protected]. For more information about PALYNZIQ, please visitwww.palynziq.com. For additional information regarding this product, please contact BioMarin Medical Information at[email protected].
About Phenylketonuria
PKU, or phenylalanine hydroxylase (PAH) deficiency, is a genetic condition affecting approximately 70,000 people in the regions of the world where BioMarin operates. This enzyme is required for the metabolism of Phe, an essential amino acid found in most protein-containing foods. If functional enzyme is not present in sufficient quantities, Phe accumulates to abnormally high levels in the blood and becomes toxic to the brain, resulting in a variety of complications including severe intellectual disability, seizures, tremors, behavioral problems and psychiatric symptoms.
As a result of newborn screening efforts implemented in the 1960s and early 1970s, virtually all individuals with PKU born after this period in countries with newborn screening programs are diagnosed at birth and treatment is implemented soon after.
PKU can be managed with a severe Phe-restricted diet, which is supplemented by low-protein modified foods and Phe-free medical foods; however, it is difficult for most individuals to adhere to the lifelong strict diet to the extent needed to achieve adequate control of blood Phe levels. Dietary control of Phe in childhood can prevent major developmental neurological toxicities, but poor control of Phe in adolescence and adulthood is associated with a range of neurocognitive disabilities with significant functional impact.
PALYNZIQ U.S. Indication and Important Safety Information
PALYNZIQ®(pegvaliase-pqpz) is a phenylalanine (Phe)-metabolizing enzyme indicated to reduce blood Phe levels in adult patients with phenylketonuria who have uncontrolled blood Phe levels greater than 600 micromol/L on existing management.
BOXED WARNING: RISK OF ANAPHYLAXIS
WARNINGS AND PRECAUTIONS
Anaphylaxis
Other Hypersensitivity Reactions
ADVERSE REACTIONS
Blood Phenylalanine Monitoring and Diet
DRUG INTERACTIONS
Effect of PALYNZIQ on Other PEGylated Products
USE IN SPECIFIC POPULATIONS
Pregnancy and Lactation
Pediatric Use
Geriatric Use
You are encouraged to report suspected adverse reactions to BioMarin at 1-866-906-6100, or to FDA at 1-800-FDA-1088 orwww.fda.gov/medwatch.
Please see accompanying fullPrescribing Information, including Boxed Warning.
About BioMarin
BioMarin is a global biotechnology company dedicated to translating the promise of genetic discovery into medicines that make a profound impact on the life of each patient. TheSan Rafael, California-based company, founded in 1997, has a proven track record of innovation with eight commercial therapies and a strong clinical and preclinical pipeline. Using a distinctive approach to drug discovery and development, BioMarin seeks to unleash the full potential of genetic science by pursuing category-defining medicines that offer new possibilities for people living with genetically defined conditions around the world. To learn more, please visitwww.biomarin.com.
Forward-Looking Statements
This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including without limitation, statements about: data from the Phase 3 PEGASUS study presented at the 15th International Congress of Inborn Errors of Metabolism, including the oral and poster presentations; the safety profile and potential benefits of PALYNZIQ for adolescents, including ability to lower blood Phe levels in adolescents aged 12-17 with phenylketonuria (PKU) compared to diet alone; the development of BioMarin's PALYNZIQ program generally, including plans to submit PEGASUS study to global health authorities during the second half of 2025 to expand the approved indication for PALYNZIQ to include the treatment of adolescents; and the continued clinical development of PALYNZIQ, including BioMarin's plans to continue to evaluate long-term results of PALYNZIQ treatment for adolescents through the ongoing extension phase of the PEGASUS trial. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: results and timing of current and planned preclinical studies and clinical trials of PALYNZIQ; any potential adverse events observed in the continuing monitoring of the patients in the clinical trials; the content and timing of decisions by the U.S. Food and Drug Administration, the European Medicines Agency, the European Commission and other regulatory authorities; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Quarterly Report on Form 10-Q for the quarter endedJune 30, 2025, as such factors may be updated by any subsequent reports. Investors are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise.
BioMarin®, BioMarin RareConnections®and PALYNZIQ®are registered trademarks of BioMarin Pharmaceutical Inc.
SOURCE BioMarin Pharmaceutical Inc.
| PALYNZIQ(n=31) | Diet only(n=17) | |
| Mean % change in blood Pheconcentration from baseline | -49.7 % | -0.3 % |
| # of participants achieving blood Phelevels ≤600 µmol/L | 16 (51.6 %) | 1 (5.9 %) |
| # of participants achieving blood Phelevels ≤360 µmol/L | 12 (38.7 %) | 0 (0 %) |
| # of participants achieving blood Phelevels ≤120 µmol/L | 6 (19.4 %) | 0 (0 %) |
| Change from baseline in intact foodprotein intake (g/kg/day) | 0.21 (107 %) | -0.02 (-10 %) |
| Change from baseline in medical foodprotein intake (g/kg/day) | -0.20 (-29 %) | 0.03 (22 %) |
| Contacts: | |
| Investors | Media |
| Traci McCarty | Katherine Powell |
| BioMarin Pharmaceutical Inc. | BioMarin Pharmaceutical Inc. |
| (415) 455-7558 | (415) 827-2968 |