A Pilot Study of Commercially Available Bowel Preparation Regimens Packaged and Ingested Via Vegan Capsules: Safety, Tolerability, Feasibility, and Preliminary Cleansing Effectiveness

The goal of this clinical trial is to learn whether bowel preparation powders used before colonoscopy can be taken as capsules instead of being mixed and drunk as a liquid. Bowel preparation is the medicine people take to clean the bowel before a colonoscopy.
This study will include adults aged 18 to 75 years who are already scheduled for an outpatient colonoscopy and who have had a colonoscopy before.
The main questions this study aims to answer are:
1. Can participants swallow and complete a large number of bowel preparation capsules with the required clear fluids?
2. Can the capsules be prepared accurately and practically by a pharmacy or by participants at home?
3. Is the capsule-based bowel preparation safe and well tolerated?
4. Does the capsule-based bowel preparation clean the bowel well enough for colonoscopy?
Participants will take approved bowel preparation products, Pico-Salax or Bi-PegLyte, in vegan hydroxypropyl methylcellulose capsules. They will take the capsules with clear fluids using a split-dose schedule before colonoscopy.
The study will happen in three parts. First, researchers will test two capsule sizes using Pico-Salax capsules prepared by a partner pharmacy. Then, researchers will test Bi-PegLyte capsules using the capsule size selected from the first part. Finally, some participants will prepare the capsules themselves at home using study instructions and materials.
Researchers will measure how many capsules and how much fluid participants complete, symptoms during preparation, safety blood tests, participant satisfaction, and bowel cleanliness during colonoscopy.

Start Date01 Aug 2026

Sponsor / Collaborator

Ottawa Hospital Research Institute

NCT07604025

/ Not yet recruitingEarly Phase 1IIT

Senna vs. Polyethylene Glycol 3350 for the Treatment of Retentive Encopresis in Children: a Randomized, Double-blinded, Study

The goal of this clinical trial is to learn which treatment is more effective for children with functional constipation (FC) and fecal incontinence (FI), also called retentive encopresis.
Functional constipation is common in children and can cause pain, embarrassment, social stress, and repeated medical visits. One of the hardest symptoms to treat is fecal incontinence. Two common treatments are polyethylene glycol 3350 (PEG), an osmotic laxative, and Senna, a plant-based stimulant laxative. PEG is often used as standard maintenance therapy, while Senna is increasingly used, especially in children with difficult or refractory constipation. However, there is not enough high-quality evidence comparing these two treatments directly in children with fecal incontinence.
The main question this study aims to answer is:
Does Senna reduce the number of fecal incontinence episodes more than PEG after 3 months of treatment? The study will also assess safety, tolerability, abdominal pain or cramping, use of rescue enemas, treatment satisfaction, and treatment compliance.
This is a prospective, randomized, double-blinded clinical trial. Children will be randomly assigned to receive either daily Senna or daily PEG for 3 months. Neither the families nor the treating medical team will know which treatment the child is receiving. Both medications will be prepared as identical-looking white powder in identical packages.
Participants will be children aged 4 to 18 years who have functional constipation according to Rome IV criteria and have fecal incontinence at least 4 times per week. Children with an organic disease that may cause fecal incontinence, such as Hirschsprung disease, spinal cord abnormalities, or anorectal malformations, will not be included.
Before starting the study medication, all participants will complete a 3-day bowel clean-out using high-dose PEG, with Pico-Salax added on the third day. After this clean-out, children will start their assigned daily treatment, either Senna or PEG. The dose will be based on age and may be adjusted by the physician according to stool consistency, stool frequency, cramping, and the child's clinical response. All families will also receive behavioral advice, including regular toilet sitting twice daily, correct toilet position using a footstool, and going to the toilet when the child feels the need.
Participants will:
* Take daily Senna or daily PEG for 3 months
* Visit the clinic at baseline, 1 month, 2 months, and 3 months
* Complete a 7-day stool and fecal incontinence diary before each visit
* Report abdominal pain, cramping, diarrhea, perianal irritation, or any other adverse events
* Return medication containers so compliance can be checked by weighing the remaining medication
* Complete satisfaction and improvement questionnaires at the 3-month visit
Outcome Measurements:
The primary outcome is the mean number of fecal incontinence episodes per week after 3 months of treatment. This will be measured using a prospective 7-day diary completed by the family before the 3-month clinic visit.
The secondary outcomes, assessed at 3 months, include:
* Change in patient-initiated toilet sitting, meaning times when the child independently says they need to defecate
* The proportion of children who reach 0-1 fecal incontinence episodes per week
* The proportion of children with any improvement, defined as at least 1 fewer fecal incontinence episode per week
* Number of rescue enemas used during the 3-month study period
* Frequency and severity of abdominal pain or cramping
* Parent-reported satisfaction with treatment using a 5-point Likert scale
* Family impression of overall improvement using a 5-point Likert scale
* The proportion of children still meeting Rome IV criteria for functional constipation
* Treatment compliance, defined as good compliance if more than 80% of doses were taken
The study plans to enroll 80 children total, with 40 children in the Senna group and 40 children in the PEG group.

Start Date01 Jul 2026

Sponsor / Collaborator

Shaare Zedek Medical Center

[+1]

IRCT20191104045328N53

/ RecruitingPhase 3IIT

Comparison of the effectiveness of Polyethylene Glycol (PEG) and Nonapick on bowel preparation in patients undergoing diagnostic colonoscopy.

Start Date20 May 2026

Sponsor / Collaborator

Shahid Beheshti University of Medical Sciences

100 Clinical Results associated with Polyethylene glycol 3350

100 Translational Medicine associated with Polyethylene glycol 3350

100 Patents (Medical) associated with Polyethylene glycol 3350

48,995

Literatures (Medical) associated with Polyethylene glycol 3350

01 Apr 2027·DEN open

Patient Characteristics Associated With Preference for 480‐mL Oral Sodium Sulfate: A Prospective Clinical Study on Bowel Cleansing Efficacy and Taste Acceptability for Total Colonoscopy

Article

Author: Shimizu, Takeshi ; Eto, Yutaka ; Yamagata, Taku ; Ito, Kei ; Sawai, Yosei ; Kanno, Yoshihide ; Sato, Hiroki ; Korekawa, Kai ; Numata, Teruyuki ; Shimada, Tomohiro

ABSTRACT:

Background and Aims:

Oral sulfate solutions (OSSs) are used for low‐volume bowel preparation but have a distinctive bitter taste. This study evaluated the efficacy and tolerability of OSSs compared with polyethylene glycol plus ascorbate (PEG‐ASC) and identified patient factors associated with favorable acceptability.

Methods:

In this prospective single‐center study, patients undergoing colonoscopy using OSSs who had used PEG‐ASC for a previous colonoscopy within 2 years were enrolled. Cleansing quality (Boston Bowel Preparation Scale [BBPS]), ingested volume, adverse events, patient preference, and taste acceptability were assessed. Outcomes were also compared between elderly (≥75 years) and non‐elderly patients.

Results:

Among 263 patients, 98% achieved satisfactory cleansing (BBPS ≥ 6). Overall, 54% preferred OSS for their next procedure. Multivariate analysis identified favorable taste acceptability as the strongest predictor of preference (odds ratio [OR], 4.88). Favorable taste acceptability tended to be associated with male sex (OR, 1.58; p = 0.09) and age ≥ 75 years (OR, 1.69; p = 0.07). Older male patients showed significantly higher favorable taste acceptability than younger female patients (63% vs. 40%; p = 0.03). Elderly patients had lower total fluid intake ( p = 0.04) and fewer adverse events ( p < 0.01), particularly nausea, while maintaining cleansing quality equivalent to non‐elderly patients.

Conclusions:

OSS provided high‐quality cleansing with a reduced intake volume. Elderly patients tended to have favorable taste acceptability for OSS, and effective cleansing was achieved with even lower total fluid intake and fewer adverse events. OSS represents an advantageous bowel preparation option for the aging population.

Trial Registration:

UMIN‐CTR: UMIN000052571.

01 Apr 2027·DEN open

Time to Confirmed Completion of Bowel Preparation as a Preprocedural Indicator of Colonoscope Insertion Difficulty: A Prospective Observational Study

Article

Author: Ueda, Hiroki ; Ishibashi, Yusuke ; Horiuchi, Kazuki

ABSTRACT:

Background and Aims:

Runway time, defined as the interval between completion of polyethylene glycol ingestion and the start of colonoscopy, has been studied as a determinant of bowel cleansing quality. However, whether the bowel preparation course itself is associated with colonoscope insertion difficulty remains unclear. We aimed to examine the associations of bowel preparation course indicators with cecal intubation time (CIT) and loop formation.

Methods:

In this single‐center prospective observational study, we enrolled consecutive patients undergoing unsedated colonoscopy and prospectively recorded four bowel preparation course indicators: time to first bowel movement, time to confirmed completion of bowel preparation, total number of bowel movements, and estimated stool volume. Multivariable linear regression analysis was performed using log‐transformed CIT as the dependent variable and adjusting for age, sex, body mass index (BMI), and endoscopist. Associations with loop formation were examined using multivariable logistic regression analysis adjusted for age, BMI, and endoscopist.

Results:

A total of 185 patients were included. Among the four indicators, only the time to confirmed completion of bowel preparation was associated with insertion difficulty. In multivariable linear regression analysis, each 30‐min increase in time to confirmed completion of bowel preparation was associated with longer CIT (exp(β), 1.139; 95% confidence interval [CI], 1.065–1.219). In multivariable logistic regression analysis, it was also associated with loop formation (odds ratio, 1.624; 95% CI, 1.129–2.360, per 30‐min increase).

Conclusions:

Time to confirmed completion of bowel preparation may serve as a simple preprocedural indicator of colonoscope insertion difficulty.

Trial Registration:

N/A.

01 Dec 2026·Techniques in Coloproctology

Comparing the efficacy of mannitol and polyethylene glycol in treating patients with poor bowel preparation: a randomized controlled clinical study

Article

Author: Zheng, S ; Deng, F ; Lin, P ; Xu, Z ; Zhang, Z ; Xia, Y ; Qian, T ; Wang, C ; Xu, L ; Wang, S ; Wang, W

BACKGROUND:

Colorectal cancer (CRC) remains a global health concern, underscoring the importance of effective bowel preparation for diagnostic procedures such as colonoscopy. This randomized controlled trial was designed to compare the efficacy and tolerability of orally administered mannitol and polyethylene glycol (PEG) solutions for repeat colonoscopy in patients with inadequate bowel preparation.

METHODS:

This prospective, open-label, noninferiority, blinded end point, randomized controlled clinical trial enrolled patients from two centers. Participants aged 18-75 years with Boston Bowel Preparation Scale (BBPS) scores ≤ 1 in any colon segment were included. The study employed a 1-L mannitol or PEG solution, with primary outcomes assessed using BBPS scores. The secondary outcomes included adverse events, taste preferences, and patient satisfaction. A simple randomization strategy was employed, and both intention-to-treat (ITT) and per-protocol (PP) analyses were conducted.

RESULTS:

A total of 134 patients were included in the study, and the trial demonstrated the noninferiority of mannitol compared to PEG in achieving adequate bowel preparation (difference 3.0%, 95% confidence interval - 5.0 to 11.0%). Mannitol exhibited favorable trends in BBPS scores, highlighting its effectiveness. The safety profiles of the two solutions were comparable, with a low incidence of adverse events (17.9% vs. 19.4%, P = 0.825). Notably, mannitol outperformed PEG in terms of patient satisfaction and a greater inclination for reuse.

CONCLUSION:

The findings suggest that orally administered mannitol is not inferior to orally administered PEG in patients with inadequate bowel preparation.

REGISTRATION NUMBER:

ClinicalTrials.gov, NCT05912114. Registered on 12/6/2023.

News (Medical) associated with Polyethylene glycol 3350

28 Feb 2026

·www.prnewswire.com

U.S. Food and Drug Administration Approves BioMarin's PALYNZIQ® (pegvaliase-pqpz) for Adolescents 12 Years of Age and Older with Phenylketonuria (PKU)

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

Clinical ResultDrug ApprovalPhase 3

27 Feb 2026

·www.biomarin.com

Treatment with PALYNZIQ led to statistically significant blood phenylalanine (Phe) lowering compared to diet alone in pivotal Phase 3 PEGASUS study

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). Table 1: Change from Baseline in Blood Phe Level (by μmol/L) Among Randomized Participants in PEGASUS Study Visit PALYNZIQ Diet Only Baseline N = 36 N = 19 Mean (standard deviation [SD]) 1025 (254) 1029 (199) Week 72 N = 32 N = 17 Mean (SD) 567 (396) 973 (234) Mean (SD; min, max) Change at Week 72 -473 (285; -22, -1133) -19 (249; 355, -634) Treatment Difference (95% CI) -409 (-579, -240) "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 www.PALYNZIQREMS.com 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 support@biomarin-rareconnections.com. For more information about PALYNZIQ, please visit www.palynziq.com. For additional information regarding this product, please contact BioMarin Medical Information at medinfo@bmrn.com. 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 REACTIONSThe 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 LactationAvailable 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 www.fda.gov/medwatch. 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 www.biomarin.com. 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. Contacts: Investors Media Traci McCarty Katherine Powell BioMarin Pharmaceutical Inc. BioMarin Pharmaceutical Inc. (415) 455-7558 (415) 827-2968 SOURCE BioMarin Pharmaceutical Inc.

29 Oct 2025

·www.prnewswire.com

FDA Accepts BioMarin's PALYNZIQ® (pegvaliase-pqpz) Supplemental Biologics License Application for Priority Review to Expand Use to Adolescents Aged 12-17 with Phenylketonuria

Application based on positive results from Phase 3 PEGASUS study, which demonstrated statistically significant blood phenylalanine (Phe) lowering compared to diet alone FDA PDUFA target action date of Feb. 28, 2026 SAN RAFAEL, Calif., Oct. 29, 2025 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the company's PALYNZIQ® (pegvaliase-pqpz) supplemental Biologics License Application (sBLA) to expand treatment to include adolescents aged 12-17 with phenylketonuria (PKU). The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of Feb. 28, 2026. "Adolescents and young adults with PKU need better options that can deliver meaningful reductions in blood Phe levels and provide greater dietary freedom," said Greg Friberg, M.D., Executive Vice President and Chief Research & Development Officer at BioMarin. "The results we observed in the PEGASUS trial demonstrated the potential PALYNZIQ can offer to help adolescents achieve guideline-recommended and even normal Phe levels, while eating significantly more protein from whole foods. For more than two decades, BioMarin has led the way in driving scientific progress in partnership with the PKU community, and we look forward to working closely with the FDA with the goal of expanding treatment with PALYNZIQ to adolescents as soon as possible." The company is also working to share these data with the European Medicines Agency with the goal of expanding treatment with PALYNZIQ to include adolescents as young as age 12 in the European Union. The sBLA 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 12-17 with PKU. These data were recently presented at the 15th International Congress of Inborn Errors of Metabolism (ICIEM) in Kyoto, Japan. PALYNZIQ is the first and only enzyme substitution therapy approved to treat adults with PKU. About PEGASUS PEGASUS is a Phase 3 multi-center open-label randomized controlled study evaluating the safety and efficacy of PALYNZIQ compared to diet alone in 55 adolescents aged 12-17 with phenylketonuria. The primary endpoints are change in blood Phe concentration and characterization of the safety profile in adolescents. Secondary endpoints include pharmacokinetics and change in total dietary protein intake. The study is being conducted in two parts: the primary treatment phase ranging from weeks 1-73 (Part 1), and the extension phase (Part 2), which lasts for up to an additional 80 weeks of monitoring for the PALYNZIQ arm and allows for crossover for those in the diet-only arm. For more information, please visit clinicaltrials.biomarin.com. 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. 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 levels in adult patients with phenylketonuria who have uncontrolled blood Phe levels greater than 600 micromol/L on existing management. BOXED WARNING: RISK OF 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 competency with self-administration, and patient's and observer's (if applicable) ability to recognize signs and symptoms of anaphylaxis and to administer auto-injectable 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 auto-injectable epinephrine, and call for emergency medical support upon its use Prescribe auto-injectable epinephrine. 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 auto-injectable 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 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 tightness, skin flushing, 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 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 auto-injectable epinephrine, and call for emergency medical support upon its use Anaphylaxis requires immediate treatment with auto-injectable epinephrine. Prescribe auto-injectable epinephrine to all patients receiving PALYNZIQ and instruct patients to carry auto-injectable epinephrine with them at all times during PALYNZIQ treatment. Prior to the first dose, instruct the patient and observer (if applicable) on how to recognize the signs and symptoms of anaphylaxis, how to properly administer auto-injectable epinephrine, and to seek immediate medical care upon its use. Consider the risks associated with auto-injectable epinephrine use when prescribing PALYNZIQ. Refer to the auto-injectable epinephrine prescribing information for complete information 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. Subsequent PALYNZIQ dose titration should be based on patient tolerability and therapeutic response Consider premedication with an H1-receptor antagonist, H2-receptor antagonist, and/or antipyretic prior to PALYNZIQ administration based upon individual patient tolerability Other Hypersensitivity Reactions Hypersensitivity reactions other than anaphylaxis have been reported in 204 of 285 (72%) patients treated with PALYNZIQ in clinical trials 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, and may include dosage adjustment, temporary drug interruption, or treatment with antihistamines, antipyretics, and/or corticosteroids 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. Advise patients to rotate injection sites with each dose 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. Advise patients not to administer PALYNZIQ into the affected area until the infection has resolved ADVERSE REACTIONS The most common adverse reactions (at least 20% of patients 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 Of the 285 patients exposed to PALYNZIQ in an induction/titration/maintenance regimen in clinical trials, 44 (15%) patients discontinued treatment due to adverse reactions. The most common adverse reactions leading to treatment discontinuation were hypersensitivity reactions (6% of patients) including anaphylaxis (3% of patients), angioedema (1% of patients), arthralgia (4% of patients), generalized skin reactions lasting at least 14 days (2% of patients), and injection site reactions (1% of patients) The most common adverse reactions leading to dosage reduction were arthralgia (15% of patients), hypersensitivity reactions (9% of patients), injection site reactions (4% of patients), alopecia (3% of patients), and generalized skin reactions lasting at least 14 days (2% of patients) The most common adverse reactions leading to temporary drug interruption were hypersensitivity reactions (14% of patients), arthralgia (13% of patients), anaphylaxis (4% of patients), and injection site reactions (4% of patients) Angioedema and serum sickness: In clinical trials, 22 out of 285 (8%) 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%) patients 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 PALYNZIQ may cause fetal harm when administered to a pregnant woman 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 Pediatric Use The safety and effectiveness of PALYNZIQ in pediatric patients have not been established Geriatric Use 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 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: BioMarin's expectations regarding its submission of the PALYNZIQ (pegvaliase-pqpz) supplemental Biologics License Application (sBLA) to expand treatment to include adolescents aged 12-17 with phenylketonuria (PKU), including expectations regarding the Prescription Drug User Fee Act (PDUFA) target action date; the safety profile and potential benefits of PALYNZIQ for adolescents, including the potential PALYNZIQ can offer to help adolescents achieve guideline-recommended and even normal Phe levels while eating significantly more protein from whole foods; the development of BioMarin's PALYNZIQ program generally, including plans to share data with the European Medicines Agency 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, including BioMarin's plans to continue to evaluate long-term results of PALYNZIQ treatment for adolescents through the ongoing extension phase of the PEGASUS trial. 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 U.S. Food and Drug Administration, the European Medicines Agency, the European Commission and other regulatory authorities; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Quarterly Report on Form 10-Q for the quarter ended September 30, 2025, as such factors may be updated by any subsequent reports. 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. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 3Clinical ResultNDAPriority ReviewDrug Approval

100 Deals associated with Polyethylene glycol 3350

External Link

KEGG	Wiki	ATC	Drug Bank
D03370	Polyethylene glycol 3350	A06AD	DB09287

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Chronic constipation	Australia	Key Pharmaceuticals Pty Ltd.	21 Nov 2012
Constipation	United States	Braintree Ltd.	18 Feb 1999

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Colonic Cancer	Phase 3	Germany	Norgine Ltd.	01 Sep 2004
Pharmaceutical aids	Phase 2	United States	FERRING BV	01 Oct 2019
Hepatitis C, Chronic	Phase 2	New Zealand	Gilead Sciences, Inc.	01 Dec 2010
Intestinal preparation	Phase 2	Germany	Norgine BV	01 May 2001
Fecal Impaction	Phase 2	United Kingdom	Norgine BV	01 Oct 2000
Colorectal Cancer	Phase 1	Romania	Norgine Ltd.	01 Apr 2011

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04708366 (Pubmed \| Ann Intern Med)	Phase 4	Intestinal preparation	665	1L PEG-ascorbate	ioyksqqhcl(ywrzgmicto) = nqypzszwqy lcjyuihupq (qusfbmexmx ) View more	Positive	01 Jun 2026
				2L PEG-ascorbate	ioyksqqhcl(ywrzgmicto) = kvbbqtuvtp lcjyuihupq (qusfbmexmx ) View more
NCT04585542 (KBindER, CTgov)	Phase 4	Hyperkalemia	37	Polyethylene Glycol 3350 (Polyethylene Glycol 3350 (MiraLax))	fdascaeqwq(cwjarnhtxk) = styykuvmmy epdbanrchs (irxosvnlxm, 0.49) View more	-	22 Apr 2026
				Sodium Polystyrene Sulfonate Oral Suspension [SPS] (Sodium Polystyrene Sulfonate (Kayexalate))	fdascaeqwq(cwjarnhtxk) = xygstxjumh epdbanrchs (irxosvnlxm, 0.42) View more
DDW2025	Not Applicable	-	2,920	NER1006	yeuddiisxg(norphgensf) = rlypntuflp jvpfbctrtc (akvuboynep ) View more	Positive	03 May 2025
NCT03298945 (CTgov)	Phase 4	Colorectal Cancer	2,239	Golytely (Golytely)	cqqcpbunxq = zsqyqjszpd zvnmdgswqv (rykkxflper, bhmfdvilxo - lvojgaxmjl) View more	-	22 Jan 2025
				Miralax (Miralax-Gatorade Prep)	cqqcpbunxq = dcdglfixha zvnmdgswqv (rykkxflper, gsffykaoog - yvlsmwflkm) View more
UEGW2024	Not Applicable	-	540	Elobixibat plus sodium picosulfate with magnesium citrate	itcxzyeitp(otvauqgcpi): difference = -1.5 (95% CI, -4.8 to 1.6) View more	Positive	13 Oct 2024
				Split-dose 2-L polyethylene glycol with ascorbic acid
NCT04210427 (CTgov)	Phase 4	Esophageal Motility Disorders \| Cystic Fibrosis	3	SmartPill Motility System & PillCam Patency Capsule+Polyethylene Glycol 3350	ngynzuxhyt(ohkmxqvwxc) = ccwxvtmbhq lkyrzvxhrr (smdzduizlh, 13) View more	-	09 Aug 2024
UEGW2023	Not Applicable	-	-	1L PEG + ASC	exlxhbchez(vtzvvggocv) = yjjrxarbev nxbhdogxyu (cgzawjnxdt ) View more	Positive	15 Oct 2023
				Placebo	exlxhbchez(vtzvvggocv) = rndwzttrln nxbhdogxyu (cgzawjnxdt ) View more
UEGW2022	Not Applicable	-	-	1L Polyethylene glycol (PEG) + ascorbic acid (ASC)	blziawpqci(kdbwpymewn) = 0.2% pqbkgdxvse (eusjlhutpo ) View more	Positive	09 Oct 2022
NCT02254486 \| NCT02273167 \| NCT02273141 (Pubmed)	Phase 3	Colonic Cancer \| Colorectal Cancer	1,028	NER1006	jescqqxfjb(ajnuayccaf) = four adverse events involving hypernatremia (0.4% of 1028), which were mild and did not require medical intervention; sodium levels returned to normal range by visit 3 qcptrgjmgk (twzxmglhnz )	-	05 Sep 2022
DDW 12022 \| DDW 22022 \| DDW 32022 \| DDW 42022 \| DDW 52022	Not Applicable	Inflammatory Bowel Diseases	-	MiralaxÂ® in 64 oz GatoradeÂ®	jjkrsylzxt(omqhobxynv) = zskvnftlyd jkajczyebl (nafwbdduul )	-	23 May 2022
				POLYTETHYLENE GLYCOL-BASED BOWEL PREPARATION (NPO)	jjkrsylzxt(omqhobxynv) = xyvrlptdup jkajczyebl (nafwbdduul )

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