Palynziq (pegvaliase-pqpz) / BioMarin - LARVOL DELTA

Immune Modulation During Palynziq® Treatment in Adults (IMPALA) (clinicaltrials.gov) - P4 | N=12 | Not yet recruiting | Sponsor: BioMarin Pharmaceutical

New P4 trial • Immune Modulation • Immunology • Metabolic Disorders • Phenylketonuria • Rare Diseases

852370: When the Trial Ends Early: Perspectives on Premature Clinical Trial Closures in Rare Disease Therapeutics (ACMG 2026) - "Medical genetics has entered a new therapeutic era, with increasing FDA approvals for rare disease treatments such as pegvaliase, vosoritide, and Skysona. Dr. Melinda Peters will offer a regulatory view on the complex aftermath of abruptly halted trials.Together, these perspectives highlight the need for sustainable, ethical frameworks to advance therapeutics in rare disease care.Learning Objectives:• Describe the evolution of therapeutic development in medical genetics and its impact on rare disease management.• Identify the regulatory, ethical, and practical challenges posed by premature clinical trial terminations.• Discuss the psychological and clinical consequences of early trial closure on affected patients and families.• Evaluate potential strategies for maintaining patient care continuity when investigational therapies are halted."

Clinical • Cognitive Disorders • Rare Diseases

SAFETY OF SEPIAPTERIN AND PEGVALIASE FOR THE TREATMENT OF PHENYLKETONURIA (PKU): A SIMULATED TREATMENT COMPARISON (STC) (ISPOR 2026) - "OBJECTIVES: PKU causes elevated blood phenylalanine (Phe) leading to neurological damage and cognitive disability. In this analysis, sepiapterin exhibited a significantly more favorable safety profile than pegvaliase. Immune reactions are prominent in pegvaliase-treated patients. As such, it has been graded a black box warning and is available only under a restricted program (Risk Evaluation and Mitigation Strategy)."

Clinical • CNS Disorders • Cognitive Disorders • Developmental Disorders • Infectious Disease • Metabolic Disorders • Musculoskeletal Pain • Phenylketonuria • Rare Diseases • Respiratory Diseases

Management of pegvaliase-related skin concerns: best practice recommendations using a modified Delphi approach. (PubMed, Mol Genet Metab) - "These internationally relevant, evidence-based recommendations provide a structured framework for managing pegvaliase-related skin concerns. Adoption of this guidance may enhance treatment adherence, mitigate adverse events, and ultimately improve patient outcomes."

Journal • Metabolic Disorders • Phenylketonuria • Rare Diseases

BioMarin Pharmaceutical…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) (PRNewswire) - "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."

FDA approval • Phenylketonuria

Pegvaliase Treatment for Adolescents With Phenylketonuria: A Multi-Site Study. (PubMed, JIMD Rep) - "Earlier initiation, when family support is typically stronger, may improve outcomes. These findings support reconsidering current age restrictions for pegvaliase therapy."

Journal • Alzheimer's Disease • Cognitive Disorders • Fatigue • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Phenylketonuria • Rare Diseases

Integration of Clinical Pharmacy Services in an Inborn Errors of Metabolism Clinic (ACMG 2026) - "Pegvaliase-pqpz (Palynziq) was the most commonly prescribed medication among patients requiring pharmacist utilization (n=86, 29.6%)... The integration of a clinical pharmacist into an inborn errors of metabolism clinic enhances patient care by ensuring timely initiation and optimization of medication therapy with the potential to reduce provider workload. By managing medication-related questions, facilitating care coordination, providing ongoing monitoring, and educating patients, pharmacists are well-suited to collaborate with an interdisciplinary team to maximize the quality of patient care. While the complexity of medication use in patients with IEM continues to expand, the inclusion and expansion of clinical pharmacy services can effectively support gaps in the medication management process."

Clinical • Cystic Fibrosis • Fabry Disease • Gaucher Disease • Genetic Disorders • Hematological Disorders • Hemophilia • Immunology • Metabolic Disorders • Phenylketonuria • Rare Diseases • Respiratory Diseases

Design of a Randomized, Double-Blind, Placebo-Controlled, Phase 3, Efficacy and Safety Trial of Repinatrabit in Adults with Phenylketonuria (ACMG 2026) - P3 | "Participants with a history of pegvaliase treatment must have at least a 4-week washout before screening... This Phase 3, randomized, placebo-controlled, 52-week trial will provide pivotal efficacy and safety data on the use of repinatrabit in adults with PKU. Enrollment criteria will enable the recruitment of a population with a broad range of disease severity and treatment history. Sponsored by Otsuka Pharmaceutical Development and Commercialization, Inc."

Clinical • P3 data • Metabolic Disorders • Phenylketonuria • Rare Diseases • SLC6A19

Nutritional Impacts of Palynziq on Patients With Phenylketonuria (PKU) (clinicaltrials.gov) - P=N/A | N=45 | Recruiting | Sponsor: Emory University | Trial completion date: Nov 2027 ➔ Dec 2028 | Trial primary completion date: Nov 2027 ➔ Dec 2028

Trial completion date • Trial primary completion date • Metabolic Disorders • Phenylketonuria • Rare Diseases

Preliminary Study of Brain Effects of Palynziq-Related Changes in Phenylalanine in Individuals With PKU (clinicaltrials.gov) - P=N/A | N=6 | Completed | Sponsor: University of Missouri-Columbia | N=13 ➔ 6 | Trial completion date: Dec 2025 ➔ Jul 2025 | Trial primary completion date: Dec 2025 ➔ Jul 2025 | Enrolling by invitation ➔ Completed

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Metabolic Disorders • Phenylketonuria • Rare Diseases

Prescription Drugs Subject to a Risk Evaluation and Mitigation Strategy: Patient Perspectives on Risk Communication and the Value of Educational Materials. (PubMed, Drug Saf) - "Gaps in patients' and caregivers' understanding of REMS programs and drug risks highlight the merits of reviewing communication materials and strategies. Clear, concise, and comprehensive educational documents could promote understanding and adherence to REMS requirements."

Journal • Infectious Disease

Investigating the Patient-Relevance of Achieving Blood Phe Thresholds in PKU: Results From an Analysis of the OPAL Study (ISPOR-EU 2025) - "The objective was to investigate the patient relevance of blood Phe reductions by exploring the association between Phe and patient-reported outcomes (PRO) in PKU. A secondary analysis was conducted using an interim data cut (March 2024) of OPAL, a phase 4, multicenter, observational study assessing the real-world safety and effectiveness of pegvaliase... Achievement of the <120 µmol/L Phe threshold was associated with improvements in health-related quality of life, suggesting that Phe threshold achievement is patient-relevant."

Clinical • Metabolic Disorders • Phenylketonuria • Rare Diseases

Estimating Healthcare Resource Use Associated With the Treatment of Phenylketonuria in the United States (ISPOR-EU 2025) - "Adults and adolescents with PKU treated with a Phe-restricted diet and MNT only incur a substantial health economic burden compared with those receiving pharmacological treatment."

Metabolic Disorders • Phenylketonuria • Rare Diseases

Cost-Utility Analysis (CUA) of Sepiapterin for Treatment of Phenylketonuria (PKU) (ISPOR-EU 2025) - "The pharmacological therapies sapropterin dihydrochloride and pegvaliase have received approvals for PKU... This CUA model reflects a clinically-accurate approach for evaluating the benefits of sepiapterin compared to sapropterin or PRD for the treatment of PKU. The approach takes into account the heterogeneity in unmet need among individuals with PKU when evaluating relative treatment benefits."

HEOR • Developmental Disorders • Mental Retardation • Metabolic Disorders • Phenylketonuria • Rare Diseases

Care of Patients With Phenylketonuria (PKU) in Germany a Claims Data Analysis From 2013 to 2023 (ISPOR-EU 2025) - "Fewer than 20% of patients received pharmacotherapy (sapropterin or pegvaliase), with a sharp decline in older age groups... PKU care shows clear age-dependent patterns in diagnostics and therapy. The results highlight the need for structured, interdisciplinary, and lifelong care."

Clinical • ADHD (Impulsive Aggression) • Cardiovascular • CNS Disorders • Depression • Developmental Disorders • Diabetes • Mental Retardation • Metabolic Disorders • Mood Disorders • Osteoporosis • Phenylketonuria • Psychiatry • Rare Diseases • Rheumatology • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

From practice to evidence: The real-world impact of PALYNZIQ (SSIEM 2023) - "Sponsored by Biomarin"

Clinical • Real-world • Real-world evidence

Tackling barriers: Journey of a centre with a single specialist to deliver PALYNZIQ (SSIEM 2023) - "Sponsored by Biomarin"

Behind the science: My PALYNZIQ®▼ experience (SSIEM 2023) - "Sponsored by Biomarin"

Design of a global, multicenter study to assess maternal, fetal, and infant outcomes of pegvaliase exposure during pregnancy and breastfeeding (SSIEM 2023) - No abstract available

Clinical • Metabolic Disorders • Phenylketonuria • Rare Diseases

OPAL: A multicenter, observational study to evaluate the real-world outcomes of pegvaliase in adults with phenylketonuria (SSIEM 2023) - No abstract available

Clinical • Observational data • Real-world • Real-world evidence • Metabolic Disorders • Phenylketonuria • Rare Diseases

OPAL: A multicenter, observational study to evaluate the real-world outcomes of pegvaliase in adults with phenylketonuria (SSIEM 2023) - No abstract available

Clinical • Observational data • Real-world • Real-world evidence • Metabolic Disorders • Phenylketonuria • Rare Diseases

OPAL: A multicenter, observational study to evaluate the real-world outcomes of pegvaliase in adults with phenylketonuria (SSIEM 2023) - No abstract available

Clinical • Observational data • Real-world • Real-world evidence • Metabolic Disorders • Phenylketonuria • Rare Diseases

A feasible point-of-care testing method for monitoring phenylalanine levels using phenylalanine ammonia lyase and a portable ammonia detection system (SSIEM 2023) - "To prevent such complications, patients with PKU must adhere to strict diet therapy and receive tetrahydrobiopterin supplementation or pegvaliase injection... This point-of-care system, designated as PheCheck, is a potential low-cost home- based Phe monitoring system. Further research is required with an improved PheCheck system to enhance the control of blood Phe levels, ease the burden on PKU patients and/or caregivers, and reduce the complications associated with PKU."

Metabolic Disorders • Phenylketonuria • Rare Diseases

OPAL: A multicenter, observational study to evaluate the real-world outcomes of pegvaliase in adults with Phenylketonuria (SSIEM 2023) - "The results of this ongoing study could provide meaningful insight into the real- world use of pegvaliase and help characterize patient outcomes associated with Phe reduction."

Clinical • Observational data • Real-world • Real-world evidence • Metabolic Disorders • Phenylketonuria • Rare Diseases

Evaluating trends in self-rated historic metabolic control and treatment history among PRISM participants (SSIEM 2023) - "Most patients reported a history of “Excellent/Good” metabolic control despite Phe levels above guideline ranges; this discordance may highlight a potential lack of insight into disease severity among adults with suboptimal blood Phe control. Differing target Phe levels between published sets of guidelines (360 vs 600 micromol/L) and changes in target Phe ranges over time may be a source of confusion when self-reporting metabolic control. AEs were observed in all patients irrespective of PKU history and most were manageable with long-term use."

Immunology • Musculoskeletal Pain