The FDA has assigned a target action date of February 28, 2026, for a potential expanded indication of pegvaliase-pqpz to include adolescents with PKU.
FDA accepts pegvaliase-pqpz sBLA to expand treatment to patients with PKU aged 12-17 years | Image credit: Contemporary Pediatrics
On October 29, 2025, the FDA accepted BioMarin Pharmaceutical Inc.'s supplemental biologics license application (sBLA) for pegvaliase-pqp (Palynziq) to expand its indication to adolescents aged 12 to 17 years with phenylketonuria (PKU). The sBLA was granted priority review designation and has been assigned a Prescription Drug User Fee Act date of February 28, 2026, for potential approval.1
Currently, according to BioMarin, pegvaliase-pqp is the first and only enzyme substitution therapy approved to treat adults with PKU. The company is also "working to share these data with the European Medicines Agency with the goal of expanding treatment with PALYNZIQ to include adolescents as young as age 12 in the European Union," it stated.
The sBLA submission is supported by data from PEGASUS, a Phase 3 multicenter, open-label, randomized controlled study that evaluated pegvaliase-pqp compared to diet alone in 55 adolescents aged 12–17 years with PKU. The trial included 2 parts:
Primary endpoints included change in blood phenylalanine (Phe) concentration and safety profile characterization, while secondary endpoints assessed pharmacokinetics and total dietary protein intake.
Results were presented at the 15th International Congress of Inborn Errors of Metabolism (ICIEM) in Kyoto, Japan. According to results announced in September 2025, pegvaliase-pqpz in adolescents aged 12-17 demonstrated statistically significant blood Phe lowering compared to diet alone.2
Of the 55 total adolescents enrolled, 36 received pegvaliase-pqpz and 19 had diet alone. 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.
After the 72-week primary treatment phase, almost half of participants in the pegvaliase-pqpz 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.
"Adolescents and young adults with PKU need better options that can deliver meaningful reductions in blood Phe levels and provide greater dietary freedom," said Greg Friberg, MD, executive vice president and chief research & development officer at BioMarin, in a press release. "The results we observed in the PEGASUS trial demonstrated the potential [pegvaliase-pqpz] can offer to help adolescents achieve guideline-recommended and even normal Phe levels, while eating significantly more protein from whole foods."1
Pegvaliase-pqpz carries a boxed warning for risk of anaphylaxis.
PKU is a rare inherited metabolic disorder. Due to deficient PAH enzyme activity, patients cannot effectively metabolize phenylalanine, an amino acid found in protein-containing foods. If untreated, toxic Phe buildup can lead to severe intellectual disability, seizures, tremors, behavioral disturbances, and psychiatric symptoms.
While early diagnosis through newborn screening and strict dietary management can prevent major developmental complications, adherence to a low-Phe diet is challenging, particularly during adolescence—a period when lapses in control can lead to cognitive and functional impairments.
In this interview conducted on May 8, 2025, Suzanne Hollander, MS, RD, LDN, discusses the importance of collaborative care in PKU and the impact of a new potential treatment.3
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