FDA Approves BioMarin's PALYNZIQ for Adolescents with PKU, Expanding Treatment Access to Ages 12 and Older
核心洞察
The FDA has approved BioMarin's supplemental Biologics License Application for PALYNZIQ (pegvaliase-pqpz) to include adolescents aged 12 and older with phenylketonuria (搜索) (PKU (搜索)).
The approval is based on the Phase 3 PEGASUS study, which demonstrated statistically significant blood phenylalanine reduction compared to diet alone in adolescents with uncontrolled PKU (搜索).
PALYNZIQ is the only enzyme substitution therapy approved for PKU (搜索) treatment, offering a genotype-independent medication that may normalize phenylalanine levels while allowing unrestricted diet.
The U.S. Food and Drug Administration has approved BioMarin Pharmaceutical's supplemental Biologics License Application for PALYNZIQ (pegvaliase-pqpz) to include pediatric patients 12 years of age and older with phenylketonuria (搜索) (PKU (搜索)). This approval marks a significant expansion of treatment options for adolescents with this rare genetic disorder, as PALYNZIQ remains the only enzyme substitution therapy approved to reduce blood phenylalanine concentrations in people with PKU.
Clinical Trial Results Drive Approval
The FDA approval is based on data from PEGASUS, a Phase 3 multi-center open-label randomized controlled study that evaluated the safety and efficacy of PALYNZIQ compared to diet alone in adolescents aged 12 to less than 18 with PKU (搜索). The study included patients who had uncontrolled blood phenylalanine concentrations greater than 600 µmol/L on existing management.
Individuals in the PALYNZIQ treatment arm showed a significant mean reduction from baseline in blood phenylalanine levels at Week 72 compared to those receiving diet-only management. The results presented at the 15th International Congress of Inborn Errors of Metabolism revealed that by the end of Part 1, almost half of participants (44.4%) reached levels below guideline recommendations.
Among those who achieved target levels, 75% had blood phenylalanine concentrations below 120 µmol/L, with an average phenylalanine reduction of 828 µmol/L, representing a 94% reduction from baseline. Nine participants whose blood phenylalanine levels dropped below 30 µmol/L (hypophenylalaninemia) were able to increase their intact protein intake by 318.1% from baseline and decrease their medical food protein intake by 55.16%. Six individuals discontinued medical food completely.
Addressing Critical Treatment Needs in Adolescence
"Adolescence is a period of increasing independence and academic demands, and represents a particularly challenging time for individuals with PKU (搜索)," said Dr. Stephanie Sacharow, Director of the Dr. Harvey Levy Program for PKU and Related Conditions at Boston Children's Hospital. "The ultra-restrictive diet required for PKU management may become unsustainable, and poor blood Phe control leads to adverse neurocognitive outcomes."
Dr. Sacharow noted that PALYNZIQ is the only genotype-independent medication that may bring phenylalanine into the normal range while allowing an unrestricted diet. She emphasized that treatment adherence is often more successful in teens under age 18 while they are living at home with family support.
Catherine Warren, Executive Director of the National PKU (搜索) Alliance, highlighted the significance of this approval: "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."
Safety Profile and Administration
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. The overall safety profile observed in adolescents showed most reactions occurring during the induction/titration phase and decreasing in frequency during the maintenance phase.
In the clinical trial of patients aged 12 to less than 18 years, 4 out of 36 (11%) PALYNZIQ-treated patients experienced one episode of anaphylaxis. Two patients (5.6%) discontinued treatment due to adverse reactions.
PALYNZIQ carries a boxed warning for anaphylaxis and is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the PALYNZIQ REMS. The drug must be administered under healthcare provider supervision for the initial dose, with patients observed for at least 60 minutes following injection.
Mechanism of Action and Global Availability
PALYNZIQ substitutes the deficient phenylalanine hydroxylase (搜索) (PAH) enzyme in PKU (搜索) with a PEGylated version of the enzyme phenylalanine ammonia lyase (搜索) to break down phenylalanine. The drug is administered using a dosing regimen designed to facilitate tolerability.
PALYNZIQ is currently approved for the treatment of PKU (搜索) in more than 35 countries worldwide. BioMarin is also seeking approval from the European Medicines Agency with the goal of expanding treatment to include adolescents as young as age 12 in the European Union.
Impact on PKU Management
PKU (搜索) affects approximately 70,000 people in the regions where BioMarin operates. The condition results from phenylalanine hydroxylase (搜索) deficiency, causing phenylalanine accumulation that becomes toxic to the brain if left untreated. This can result in severe intellectual disability, seizures, tremors, behavioral problems, and psychiatric symptoms.
Traditional PKU (搜索) management requires adherence to a severe phenylalanine-restricted diet supplemented by low-protein modified foods and phenylalanine-free medical foods. However, most individuals find it difficult to adhere to this strict diet to the extent needed for adequate blood phenylalanine control. Poor phenylalanine control in adolescence and adulthood is associated with neuropsychological deficits and functional impairment.
"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 (搜索)," said Dr. Greg Friberg, 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."