Pegvaliase-PQPZ

Palynziq is the only enzyme substitution therapy approved to reduce blood phenylalanine concentrations in individuals with phenylketonuria. Credit: Jack_the_sparrow / Shutterstock.com. BioMarin Pharmaceutical has received the US Food and Drug Administration (FDA) approval for its supplemental biologics licence application (sBLA) for Palynziq’s (pegvaliase-pqpz) use in adolescents aged 12 and above with phenylketonuria (PKU). This makes Palynziq the only enzyme substitution therapy that received approval to reduce blood phenylalanine (Phe) concentrations in individuals with PKU. The approval follows data from PEGASUS, a Phase III randomised controlled, open-label, multi-centre trial assessing the efficacy and safety of Palynziq compared to dietary management alone in adolescents with uncontrolled blood Phe levels above 600µmol/L. By the end of Part I, 44.4% of participants achieved Phe concentrations below guideline recommendations; within this group, 75% fell below 120µmol/L, and the mean Phe reduction reached 828µmol/L, corresponding to a 94% decrease from baseline. For nine participants who reached hypophenylalaninaemia, intact protein intake increased by 318.1% from baseline while medical food protein intake fell by 55.16%. Six individuals discontinued medical food entirely. The most common adverse reactions among adolescents included arthralgia, dizziness, fatigue, hypersensitivity reactions, nausea, pyrexia and vomiting. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence Most side effects occurred during induction/titration phases and declined during maintenance. BioMarin’s executive vice-president and chief research and development officer Greg Friberg said: “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 the introduction of the first two treatment options for this inherited metabolic condition that otherwise requires lifelong adherence to a rigid medical diet. “We are proud to build on this legacy by expanding Palynziq’s approval to adolescents aged as young as 12 [years], which will allow even more people with PKU the prospect of achieving substantially lower Phe levels.” BioMarin is seeking European Medicines Agency (EMA) approval to broaden Palynziq’s use to adolescents aged 12 years and above in the European Union. In May 2025, BioMarin agreed to acquire Inozyme Pharma for $4.00 per share in a $270m all-cash transaction.

Treatment with PALYNZIQ led to statistically significant blood phenylalanine (Phe) lowering compared to diet alone in pivotal Phase 3 PEGASUS study PALYNZIQ is the only enzyme substitution therapy approved for the treatment of people with PKU SAN RAFAEL, Calif., Feb. 27, 2026 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today announced that the U.S. Food and Drug Administration (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. Dr. Stephanie Sacharow has participated in speaking engagements and served on advisory boards for BioMarin. About PALYNZIQ PALYNZIQ substitutes the deficient phenylalanine hydroxylase (PAH) enzyme in PKU with a PEGylated version of the enzyme phenylalanine ammonia lyase to break down Phe. PALYNZIQ is administered using a dosing regimen designed to facilitate tolerability; PALYNZIQ's safety profile consists primarily of immune-mediated responses, which can include anaphylaxis, for which robust risk management measures effective in clinical trials are in place. See the full Prescribing Information, which includes a Boxed Warning. PALYNZIQ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the PALYNZIQ REMS, because of the risk of anaphylaxis. Further information, including a list of qualified pharmacies, is available at or by telephone 1-855-758-REMS (1-855-758-7367). PALYNZIQ is approved for the treatment of PKU in more than 35 countries worldwide. Patient Support Accessing PALYNZIQ To reach a BioMarin RareConnections® Case Manager, please call, toll-free, 1-866-906-6100 or e-mail [email protected]. For more information about PALYNZIQ, please visit . For additional information regarding this product, please contact BioMarin Medical Information at [email protected]. About Phenylketonuria PKU, or phenylalanine hydroxylase (PAH) deficiency, is a genetic condition affecting approximately 70,000 people in the regions of the world where BioMarin operates. The PAH enzyme is required for the metabolism of Phe, an essential amino acid found in most protein-containing foods. If functional enzyme is not present in sufficient quantities, Phe accumulates to abnormally high levels in the blood and becomes toxic to the brain, resulting in a variety of complications including severe intellectual disability, seizures, tremors, behavioral problems and psychiatric symptoms. As a result of newborn screening efforts implemented in the 1960s and early 1970s, virtually all individuals with PKU born after this period in countries with newborn screening programs are diagnosed at birth and treatment is implemented soon after. PKU can be managed with a severe Phe-restricted diet, supplemented by low-protein modified foods and Phe-free medical foods; however, it is difficult for most individuals to adhere to this strict diet to the extent needed to achieve adequate control of blood Phe levels. Dietary control of Phe in childhood can prevent major developmental issues and neurological consequences, but poor Phe control in adolescence and adulthood is associated with a range of neuropsychological deficits and functional impairment. PALYNZIQ U.S. Indication and Important Safety Information PALYNZIQ® (pegvaliase-pqpz) is a phenylalanine (Phe)-metabolizing enzyme indicated to reduce blood Phe concentrations in adult and pediatric patients 12 years of age and older with phenylketonuria (PKU) who have uncontrolled blood Phe concentrations greater than 600 micromol/L (10 mg/dL) on existing management. BOXED WARNING: ANAPHYLAXIS Anaphylaxis has been reported after administration of PALYNZIQ and may occur at any time during treatment. Administer the initial dose of PALYNZIQ under the supervision of a healthcare provider equipped to manage anaphylaxis, and closely observe patients for at least 60 minutes following injection. Prior to self-injection, confirm patient's and observer's (if applicable) ability to recognize signs and symptoms of anaphylaxis and to administer epinephrine, if needed. Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during PALYNZIQ treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after PALYNZIQ administration, should be able to administer epinephrine, and call for emergency medical support upon its use. Prescribe epinephrine for all patients treated with PALYNZIQ. Prior to the first dose, instruct the patient and observer (if applicable) on its appropriate use. Instruct the patient to seek immediate medical care upon its use. Instruct patients to carry epinephrine with them at all times during PALYNZIQ treatment. PALYNZIQ is available only through a restricted program called PALYNZIQ REMS (Risk Evaluation and Mitigation Strategy). Further information, including a list of qualified pharmacies, is available at PALYNZIQREMS.com or by telephone at 1-855-758-REMS (1-855-758-7367). WARNINGS AND PRECAUTIONS Anaphylaxis Signs and symptoms of anaphylaxis reported include syncope, hypotension, hypoxia, dyspnea, wheezing, chest discomfort/chest tightness, tachycardia, angioedema (swelling of face, lips, eyes, tongue), throat swelling or tightness, flushed or red skin, rash, urticaria, pruritus, and gastrointestinal symptoms (vomiting, nausea, diarrhea). Anaphylaxis generally occurred within 1 hour after injection; however, delayed episodes occurred up to 48 hours after PALYNZIQ administration. Consider the risks and benefits of readministering PALYNZIQ following an episode of anaphylaxis. If the decision is made to readminister PALYNZIQ, administer the first dose under the supervision of a healthcare provider equipped to manage anaphylaxis and closely observe the patient for at least 60 minutes following the dose. In clinical trials of primarily adult patients with an induction/titration/maintenance dosage regimen, 29/285 (10%) experienced a total of 42 anaphylaxis episodes. In a clinical trial of patients 12 to less than 18 years of age, 4/36 (11%) of PALYNZIQ-treated patients experienced 1 episode of anaphylaxis. Other Hypersensitivity Reactions Management of hypersensitivity reactions should be based on the severity of the reaction, recurrence of the reaction, and the clinical judgment of the healthcare provider. In clinical trials of primarily adult patients taking PALYNZIQ, hypersensitivity reactions, other than anaphylaxis, were reported in 204/285 (72%) of patients. In a clinical trial of patients 12 to less than 18 years old taking PALYNZIQ, these reactions were reported in 12 out of 36 (33%) of patients. Injection Site Infections Serious injection site infections including abscess, cellulitis, necrosis, and ulcer have been reported. Some cases required hospitalization, surgical debridement, intravenous antibiotics, and discontinuation of PALYNZIQ. Provide proper training to patients and/or caregivers on the use of aseptic injection technique, injection site rotation and to check the site for redness, swelling, or tenderness. Instruct patients to contact their healthcare provider if signs or symptoms of an infection develop, persist, or worsen. Hypophenylalaninemia (HypoPhe) Some patients have experienced HypoPhe; monitor blood Phe levels periodically during treatment. Frequent blood Phe monitoring is recommended in the pediatric population. For blood Phe concentrations below 30 micromol/L, the dosage of PALYNZIQ may be reduced and/or dietary protein and Phe intake may be modified to maintain blood Phe concentrations within a clinically acceptable range and above 30 micromol/L. ADVERSE REACTIONS The most common adverse reactions in clinical trials of primarily adult patients (at least 20% in either treatment phase) were injection site reactions, arthralgia, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, nausea, abdominal pain, vomiting, cough, oropharyngeal pain, pruritus, diarrhea, nasal congestion, fatigue, dizziness, and anxiety. Arthralgia: In clinical trials, 245 out of 285 (86%) primarily adult patients experienced episodes consistent with arthralgia (includes back pain, musculoskeletal pain, pain in extremity, and neck pain). Injection site reactions were reported as early as after the first dose of PALYNZIQ and occurred at any time during treatment. Generalized Skin Reactions: In clinical trials, 134 out of 285 (47%) primarily adult patients treated with PALYNZIQ experienced generalized skin reactions (not limited to the injection site) lasting at least 14 days. Angioedema and serum sickness: In clinical trials, 22 out of 285 (8%) primarily adult patients experienced 45 episodes of angioedema (symptoms included: pharyngeal edema, swollen tongue, lip swelling, mouth swelling, eyelid edema, and face edema) occurring independent of anaphylaxis. In clinical trials, serum sickness was reported in 7 out of 285 (2%) primarily adult patients. In the clinical trials, adverse reactions were associated with treatment discontinuation, dosage reduction and temporary drug interruption. In the 285 primarily adult patients exposed to PALYNZIQ in an induction/titration/maintenance regimen in clinical trials, 44 (15%) patients discontinued treatment due to adverse reactions. Pediatric Patients: In a clinical study of 55 patients aged 12 to less than 18 years of age, the most common adverse reactions (at least 20% and greater than in control) were injection site reactions, arthralgia, headache, pyrexia, hypersensitivity reactions, dizziness, nausea, vomiting, fatigue, and pain in extremity. Two patients (5.6%) discontinued treatment due to adverse reactions. Blood Phenylalanine Monitoring and Diet Obtain blood Phe concentrations every 4 weeks until a maintenance dosage is established. Periodically monitor blood Phe concentrations during maintenance therapy. Counsel patients to monitor dietary protein and Phe intake, and adjust as directed by their healthcare provider. DRUG INTERACTIONS Effect of PALYNZIQ on Other PEGylated Products In a single-dose study of PALYNZIQ in adult patients with PKU, two patients receiving concomitant injections of medroxyprogesterone acetate suspension (a formulation containing PEG 3350) experienced a hypersensitivity reaction. One of the two patients experienced anaphylaxis The clinical effects of concomitant treatment with different PEGylated products are unknown. Monitor patients treated with PALYNZIQ and concomitantly with other PEGylated products for hypersensitivity reactions including anaphylaxis USE IN SPECIFIC POPULATIONS Pregnancy and Lactation Available data do not establish an increased risk of adverse developmental outcomes to the fetus exposed to PALYNZIQ. Advise women who are exposed to PALYNZIQ during pregnancy or who become pregnant within one month following the last dose of PALYNZIQ that there is a pregnancy surveillance program that monitors pregnancy outcomes. Healthcare providers should report PALYNZIQ exposure and encourage these patients to report their pregnancy to BioMarin (1-866-906-6100). Monitor blood Phe levels in breastfeeding women treated with PALYNZIQ to ensure maintenance of blood Phe <360 micromol/L. Adjust dosage and/or dietary protein and Phe intake as needed to avoid concentrations below 30 micromol/L. Pediatric & Geriatric Use: The safety and effectiveness of PALYNZIQ in pediatric patients from birth to less than 12 years have not been established. Clinical studies of PALYNZIQ did not include patients aged 65 years and older. You are encouraged to report suspected adverse reactions to BioMarin at 1-866-906-6100, or to the FDA at 1-800-FDA-1088 or . Please see accompanying full Prescribing Information, including Boxed Warning. About BioMarin BioMarin is a leading, global rare disease biotechnology company focused on delivering medicines for people living with genetically defined conditions. Founded in 1997, the San Rafael, California-based company has a proven track record of innovation, with eight commercial therapies and a strong clinical and preclinical pipeline. Using a distinctive approach to drug discovery and development, BioMarin seeks to unleash the full potential of genetic science by pursuing category-defining medicines that have a profound impact on patients. To learn more, please visit . Forward-Looking Statements This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including without limitation, statements about: the approval of BioMarin's supplemental Biologics License Application (sBLA) for PALYNZIQ for adolescents 12 years of age and older with phenylketonuria (PKU) by the U.S. Food and Drug Administration (FDA), including the safety profile and potential benefits of PALYNZIQ for adolescents and the potential to fundamentally change the way adolescents manage PKU in their daily lives; BioMarin's work with the European Medicines Agency (EMA) with the goal of expanding treatment with PALYNZIQ to include adolescents as young as age 12 in the European Union; and the continued clinical development of PALYNZIQ. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others, results and timing of current and planned preclinical studies and clinical trials of PALYNZIQ; any potential adverse events observed in the continuing monitoring of the patients in the clinical trials; the content and timing of decisions by the FDA, the EMA, the European Commission and other regulatory authorities, and those factors detailed in BioMarin's filings with the Securities and Exchange Commission (SEC), including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Annual Report on Form 10-K for the year ended December 31, 2025, as such factors may be updated by any subsequent filings with the SEC. Investors are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise. BioMarin®, BioMarin RareConnections® and PALYNZIQ® are registered trademarks of BioMarin Pharmaceutical Inc. SOURCE BioMarin Pharmaceutical Inc. 21% more press release views with Request a Demo