BioMarin Pharmaceutical Inc. announced positive topline results from its Phase 3 PEGASUS trial evaluating Palynziq (pegvaliase-pqpz) in adolescents with phenylketonuria (PKU), potentially expanding treatment options for younger patients with this rare metabolic disorder.
The study met its primary efficacy endpoint, demonstrating a statistically significant reduction in blood phenylalanine (Phe) levels in adolescents aged 12-17 with PKU compared to diet management alone. Safety results were consistent with the known profile of the medication, which is already approved for adult patients.
Understanding PKU and Current Treatment Landscape
Phenylketonuria is a rare, inherited metabolic disorder affecting approximately 70,000 people in regions where BioMarin operates. The condition is characterized by the body's inability to break down phenylalanine, an essential amino acid found in most protein-containing foods, due to a deficiency in the phenylalanine hydroxylase (PAH) enzyme.
Without treatment, Phe accumulates to toxic levels in the blood, potentially causing severe neurological complications including intellectual disability, seizures, behavioral problems, and psychiatric symptoms. Since the implementation of newborn screening programs in the 1960s and 1970s, most individuals with PKU are diagnosed at birth, allowing for early intervention.
Traditional management of PKU involves a severely restricted diet low in phenylalanine, supplemented with modified foods and Phe-free medical formulas. However, maintaining strict dietary control is challenging for most patients, particularly during adolescence when poor control can lead to significant neurocognitive disabilities.
The PEGASUS Trial Design and Results
The Phase 3 PEGASUS trial was a multi-center, open-label, randomized controlled study evaluating Palynziq compared to diet alone in 55 adolescents aged 12-17 with PKU. The primary endpoints included changes in blood Phe concentration and characterization of the safety profile in this younger population. Secondary endpoints measured changes in total dietary protein intake and pharmacokinetics.
The study was conducted in two parts: a primary treatment phase from weeks 1-73 (Part 1) and an extension phase (Part 2) lasting up to an additional 80 weeks, which allowed for crossover for participants in the diet-only arm.
Dr. Greg Friberg, Executive Vice President and Chief Research & Development Officer at BioMarin, commented on the significance of these findings: "For more than two decades, BioMarin has made strides for people with PKU – pioneering the first treatment, bringing a meaningful new option in PALYNZIQ, and continuing to innovate as we advance our research pipeline. We are encouraged to see these positive data that build on that legacy and show how PALYNZIQ can make an impact for adolescents as they begin their transition to adult living."
How Palynziq Works
Palynziq represents a novel approach to PKU management. The medication substitutes the deficient phenylalanine hydroxylase enzyme with a PEGylated version of the enzyme phenylalanine ammonia lyase to break down Phe. It is administered using a carefully designed dosing regimen to facilitate tolerability.
The therapy's safety profile primarily consists of immune-mediated responses, which can include anaphylaxis. For this reason, robust risk management measures that proved effective in clinical trials remain in place for all patients.
Current Regulatory Status and Future Plans
Palynziq is currently approved to reduce blood Phe concentrations for adults in the United States, for people 16 and older in the European Union, Canada, and Brazil, and for people 15 and older in Japan with PKU who have uncontrolled blood Phe concentrations greater than 600 micromol/L despite existing management approaches.
BioMarin plans to present detailed results from the PEGASUS study at an upcoming medical meeting and will submit the data to global health authorities later this year to request a label expansion for Palynziq to include adolescents.
Safety Considerations
The most common adverse reactions observed in previous clinical trials of Palynziq include injection site reactions, arthralgia, hypersensitivity reactions, headache, generalized skin reactions, nausea, abdominal pain, and vomiting.
Due to the risk of anaphylaxis, Palynziq is available only through a restricted program called PALYNZIQ REMS (Risk Evaluation and Mitigation Strategy). Patients receiving Palynziq are prescribed auto-injectable epinephrine and instructed to carry it with them at all times during treatment.
Market Impact
The positive results from the PEGASUS trial represent a significant advancement in BioMarin's efforts to expand treatment options for younger patients with PKU. If approved, the label expansion would allow adolescents to benefit from enzyme replacement therapy during a critical developmental period when dietary compliance often becomes more challenging.
BioMarin's stock showed a modest increase following the announcement, reflecting investor confidence in the company's continued leadership in rare disease therapeutics.
For patients and families affected by PKU, these results offer hope for improved management options during the challenging adolescent years, potentially reducing the burden of strict dietary control while maintaining appropriate blood Phe levels.
