Palynziq (pegvaliase-pqpz) / BioMarin - LARVOL DELTA

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

Metabolic and Biochemical Changes Associated with Long-Term Pegvaliase Therapy in Adults with Phenylketonuria (SSIEM 2023) - "Notable changes in energy needs and metabolic control were found in adults with PKU receiving long-term management with pegvaliase. Consistent monitoring of Phe and dietary intake remain important to prevent hypophenylalanemia and nutrient deficiencies as patients adapt to unrestricted diets. Future analysis of body composition is needed to clarify changes in energy needs."

Clinical • Metabolic Disorders • Phenylketonuria • Rare Diseases

New perspectives in PKU management – The change we can see (SSIEM 2023) - "Adverse events should also bereported to BioMarin on + 1 415 506 6179 or drugsafety@bmrn.com.PALYNZIQ® (pegvaliase) is indicated for the treatment of patients with PKU aged 16years and older who have inadequate blood phenylalanine control (bloodphenylalanine levels greater than 600 μmol/L) despite prior management withavailable treatment options.This will contain information on PALYNZIQ® which is not licensed in Israel, but islicensed in the European Union. Refer to your local Prescribing Information prior tousing PALYNZIQ®.This symposium is intended for Healthcare Professionals registered for SSIEM 2023."

FDA Accepts BioMarin's PALYNZIQ (pegvaliase-pqpz) Supplemental Biologics License Application for Priority Review to Expand Use to Adolescents Aged 12-17 with Phenylketonuria (PRNewswire) - "The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of Feb. 28, 2026....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."

FDA filing • PDUFA • Priority review • Phenylketonuria

Patient Perceptions of and Experiences with Risk Evaluation and Mitigation Strategies. (PubMed, Clin Pharmacol Ther) - "To understand patients' and caregivers' perception of and experiences with REMS programs with elements to assure safe use, we conducted semi-structured interviews from March 2022 to July 2023 with 135 patients or caregivers of patients who had used alemtuzumab (Lemtrada), ambrisentan (Letairis), clozapine (Clozaril), isotretinoin (Accutane), lenalidomide (Revlimid), pegvaliase (Palynziq), or sodium oxybate (Xyrem/Xywav). Among 135 participants, five key themes emerged: (1) Participants were knowledgeable about REMS-associated drug risks and requirements; (2) some participants had difficulty finding prescribers, particularly for clozapine; (3) administrative burdens related to REMS implementation were a source of frustration, with satisfaction higher when care coordination support was provided; (4) emotional and logistical challenges were identified with pregnancy- and clozapine-related testing; and (5) participants desired similar engagement around risks not..."

Journal

Global considerations for lifelong management and therapeutic development for phenylketonuria. (PubMed, Genet Med) - "Several new therapies are being evaluated for the treatment of PKU, offering the potential to address unmet needs. Global availability of NBS programs, access to treatments, and a tenacious commitment to treatment-for-life are expected to improve outcomes for individuals with PKU across geographic regions."

Journal • Review • Alzheimer's Disease • Cognitive Disorders • Metabolic Disorders • Phenylketonuria • Rare Diseases

GSC002874, a highly potent inhibitor of SLC6A19, for treatment of phenylketonuria (ENDO 2025) - "For the classic PKU cohort accounting for over 60 percent of cases, the only approved drug is pegvaliase; however, it is associated with inconvenient dosing and side effects...In an PAH pR408W PKU mouse model with its mouse SLC6A19 replaced by human orthologue, GSC002874 significant decreased phenylalanine level in plasma at lower dosage that of JNT-517...GSC002874 also displayed good safety window in 14-day toxicology study in rats. GSC002874 is under active IND-enabling studies and expected to enter clinic in early 2026."

Genetic Disorders • Metabolic Disorders • Phenylketonuria • Rare Diseases • SLC6A19

GSC002874, a highly potent inhibitor of SLC6A19, for treatment of phenylketonuria (ENDO 2025) - "For the classic PKU cohort accounting for over 60 percent of cases, the only approved drug is pegvaliase; however, it is associated with inconvenient dosing and side effects...In an PAH pR408W PKU mouse model with its mouse SLC6A19 replaced by human orthologue, GSC002874 significant decreased phenylalanine level in plasma at lower dosage that of JNT-517...GSC002874 also displayed good safety window in 14-day toxicology study in rats. GSC002874 is under active IND-enabling studies and expected to enter clinic in early 2026."

Genetic Disorders • Metabolic Disorders • Phenylketonuria • Rare Diseases • SLC6A19

Toxicity spectrum of pegvaliase: A pharmacovigilance analysis using the FAERS database. (PubMed, Orphanet J Rare Dis) - "We mined and analyzed the AE signals of pegvaliase based on the FAERS database, it turned out that they were generally consistent with the drug inserts and clinical trial results. However, potential new AE signals were revealed, providing a basis for the identification of adverse reactions in the clinical setting."

Adverse events • Journal • Musculoskeletal Pain

Long-term management strategies for pegvaliase use in phenylketonuria: Lessons learned from the phase 3 PRISM open-label extension study. (PubMed, Genet Med) - P3 | "These analyses establish how tolerization presents clinically and suggest a staged therapeutic approach: (1) tolerance induction; (2) diet liberalization; (3) gradual dose adjustment."

Journal • P3 data • CNS Disorders • Developmental Disorders • Mental Retardation • Metabolic Disorders • Phenylketonuria • Psychiatry • Rare Diseases

Considerations for Health Economic Modeling in Phenylketonuria (PKU): Insights From a Modified Delphi Panel (ISPOR 2025) - "In Round 2, consensus was reached on 6/10 questions, including on age ranges when Phe levels are typically maintained, safety of Phe 30-120 µmol/L with sufficient protein intake, mechanisms underlying the association between PKU and chronic comorbidities, possibility of dietary-Phe tolerance challenges at Phe 240-299 µmol/L, and possibility of resuming pegvaliase after discontinuation... Findings from this study could inform future CEAs in PKU by establishing expert consensus on outcomes to include, as well as clinically-accurate modeling of such outcomes. These insights address the limitations in previous CEAs of PKU treatments."

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