BioMarin Pharmaceutical announced that the FDA has approved the company's supplemental Biologics License Application (sBLA) for PALYNZIQ® (pegvaliase-pqpz) to include pediatric patients 12 years of age and older with phenylketonuria (PKU). PALYNZIQ is the only enzyme substitution therapy approved to reduce blood phenylalanine (Phe) concentrations in people with PKU.
"Adolescence is a period of increasing independence and academic demands, and represents a particularly challenging time for individuals with PKU. The ultra-restrictive diet required for PKU management may become unsustainable, and poor blood Phe control leads to adverse neurocognitive outcomes. PALYNZIQ is the only genotype-independent medication which may bring Phe into the normal range while allowing an unrestricted diet," said Stephanie Sacharow, M.D., Director, Dr. Harvey Levy Program for PKU and Related Conditions, Boston Children's Hospital. "In my clinic we have found that PALYNZIQ treatment adherence is even more successful in teens under age 18, while they are living at home with family support, and this approval allows us to extend this therapeutic option to adolescents who may benefit most."
The FDA approval is based on data from PEGASUS, a Phase 3 multi-center open-label randomized controlled study evaluating the safety and efficacy of PALYNZIQ compared to diet alone in adolescents aged 12 to <18 with PKU who had uncontrolled blood Phe concentrations greater than 600 µmol/L on existing management. Individuals in the PALYNZIQ arm showed a significant mean reduction from baseline in blood Phe levels at Week 72 compared to those in the diet only arm (Table 1).
“Today's FDA approval for PALYNZIQ is an important step forward for the PKU community, providing a new option for adolescents ages 12 and older that has the potential to improve daily PKU management," said Catherine Warren, Executive Director of the National PKU Alliance. "Adolescence is a time of major change for people living with PKU, and having PALYNZIQ available better sets teenagers up for success with managing their blood phenylalanine levels as they navigate the transition into adulthood."
As was recently presented at the 15th International Congress of Inborn Errors of Metabolism, by the end of Part 1 almost half of participants (44.4%) reached levels below guideline recommendations. Of those individuals, 75% were below 120 µmol/L and their average Phe reduction was 828 µmol/L (94% reduction in blood Phe from baseline). Nine participants whose blood Phe levels were below 30 µmol/L (hypophenylalaninemia) were able to increase their intact protein intake by 318.1% from baseline (SD=195.4; min=1.42, max=542.5) and decrease their intake of medical food protein by 55.16% (SD=56.4; min=-100, max=60.3); six individuals discontinued medical food completely.
The most common adverse reactions (≥20%) with PALYNZIQ in adolescents were injection site reactions, arthralgia, headache, pyrexia, hypersensitivity reactions, dizziness, nausea, vomiting, fatigue and pain in extremity. As in previous clinical studies, the overall safety profile of PALYNZIQ observed in adolescents showed most reactions occurring in the induction/titration phase and decreasing in frequency during the maintenance phase.
"Over the past two decades, BioMarin has been working hand-in-hand with the medical and advocacy communities to improve the lives of people living with PKU, including introduction of the first two treatment options for this inherited metabolic condition that otherwise requires lifelong adherence to a rigid medical diet," said Greg Friberg, M.D., Executive Vice President and Chief Research & Development Officer at BioMarin. "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."
The company is also seeking approval from the European Medicines Agency with the goal of expanding treatment with PALYNZIQ to include adolescents as young as age 12 in the European Union.
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