Stephanie Sacharow, MD, highlights the benefits of Palynziq to treat PKU

In a recent discussion, Stephanie Sacharow, MD, director at Boston Children’s Hospital, discussed the clinical impact and life-altering potential of the FDA’s expanded approval of Palynziq (pegvaliase-pqpz; BioMarin) for adolescents.

In the clinical landscape of phenylketonuria (PKU), managing blood phenylalanine (Phe) levels in adolescents has long been a significant challenge for pediatricians and metabolic specialists. Sacharow highlighted the critical importance of the FDA approval of Palynziq for pediatric patients 12 years and older. This expansion of the drug’s indication marks a transformative shift in care, moving beyond the traditional reliance on highly restrictive, often unsustainable diets.

As children transition into adolescence, adherence to the standard PKU diet, which requires severe protein restriction and the consumption of specialized medical foods, tends to decline significantly. This period of life is defined by a growing desire for independence and a social life that often revolves around food.

When adolescents disengage from their diet, their blood Phe levels can rise to toxic concentrations, leading to adverse neurocognitive outcomes, psychiatric symptoms, and behavioral problems. Sacharow emphasized that being on a PKU diet is a considerable stressor for this age group, impacting their social development and overall mental health.

The clinical data supporting Palynziq’s use in adolescents are compelling. In the phase 3 PEGASUS trial, which included patients aged 12 to 17 years with Phe concentrations greater than 600 µmol/L, the treatment demonstrated a significant reduction in mean blood Phe levels compared with diet alone.

Notably, nearly half of the participants reached guideline-recommended or even normal Phe levels. For those achieving these targets, the dietary liberalization was profound, with some patients increasing their natural protein intake by over 300% while simultaneously reducing their dependence on medical formula.

One of the unique advantages of Palynziq is that it is a genotype-independent enzyme substitution therapy. This means it can be effective even for patients with severe classic PKU who have little to no native enzyme activity, a population that historically has had few pharmacologic options. However, Sacharow and other experts stress that safety monitoring remains paramount. Because PALYNZIQ carries a boxed warning for anaphylaxis, initial doses must be administered under medical supervision, and all patients must carry an auto-injectable epinephrine device.

Ultimately, Sacharow noted that treatment adherence with Palynziq appears particularly successful in the under–18 years population. Because these patients are typically still living at home, they benefit from consistent family support during the induction and titration phases.

By introducing this therapy during the teenage years, clinicians can help stabilize metabolic control before the transition to the more independent environment of college or the workforce, providing these young patients with a path toward a more normal quality of life.

Disclosure: BioMarin Pharmaceutical Inc.

Reference

US Food and Drug Administration approves BioMarin’s Palynziq (pegvaliase-pqpz) for adolescents 12 years of age and older with phenylketonuria (PKU). News release. BioMarin. February 27, 2026. Accessed March 2, 2026. https://www.biomarin.com/news/press-releases/u-s-food-and-drug-administration-approves-biomarins-palynziq-pegvaliase-pqpz-for-adolescents-12-years-of-age-and-older-with-phenylketonuria-pku/