Palynziq (pegvaliase-pqpz) / BioMarin - LARVOL DELTA

Physician Understanding and Perceptions of Risk Communication Related to Drugs Covered by Risk Evaluation and Mitigation Strategy Programs. (PubMed, Pharmacoepidemiol Drug Saf) - "While physicians largely expressed awareness of REMS testing requirements and found REMS programs to be valuable sources of risk communication, they would like more information on managing side effects, more accessible information on REMS requirements, integration of REMS programs with EMRs, and timely updates to REMS materials as new safety information emerges."

Journal

Global Trends in Phenylketonuria Treatment Research, 2000-2025: Bibliometric Analysis. (PubMed, Online J Public Health Inform) - "Over the past 2 decades, treatment strategies have evolved from strict dietary phenylalanine restriction to include pharmacological therapies such as tetrahydrobiopterin and, more recently, enzyme substitution with pegvaliase...Future research should prioritize longitudinal multiomics investigations, targeted metabolic correction technologies, gene-based therapeutic approaches, and enhanced international collaboration, particularly to strengthen diagnosis and management capacities in low- and middle-income regions. Such efforts will be critical to advancing global standards of PKU care."

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

Mediterranean PAH Stratification in Phenylketonuria: Tracing Historical Maps to Point Toward Clinical Phenotype and Obesity Risk. (PubMed, Genes (Basel)) - "PAH mutational stratification serves as a contemporary reflection of historical migratory maps. Incorporating regional and genotypic mapping provides a precision medicine framework to anticipate phenotype severity, optimize therapeutic management, and tailor long-term obesity risk monitoring."

Journal • Retrospective data • Genetic Disorders • Metabolic Disorders • Obesity • Phenylketonuria • Rare Diseases

Bone mineral density in participants with phenylalanine hydroxylase (PAH) deficiency: a report from the PHEFREE rare disorders consortium. (PubMed, Mol Genet Metab) - "20 adults (37%) reported receiving enzyme replacement therapy with pegvaliase...Whether novel therapeutics, that both correct hyperphenylalaninemia and allow increased dietary intact protein intake, will impact bone mineralization is yet unknown. Longitudinal monitoring of BMD throughout the lifespan is warranted."

Journal • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Phenylketonuria • Rare Diseases • Rheumatology

Clinical practice considerations for restarting pegvaliase in adults with phenylketonuria. (PubMed, Mol Genet Metab Rep) - "AEs were reported (eg, injection site reactions, rash, and arthralgia) but were milder compared to the previous treatment course in most cases and some individuals responded at lower doses or after shorter treatment duration. Restarting pegvaliase should be considered as part of a shared decision-making process for individuals seeking to further optimize outcomes."

Journal • Metabolic Disorders • Mood Disorders • Musculoskeletal Pain • Obstetrics • Phenylketonuria • Psychiatry • Rare Diseases

Targeting Mutant Phenylalanine Hydroxylase With Pyrimidine-Triazole Conjugates: A Primary Framework for Candidate Chaperone-Based Strategies in Phenylketonuria. (PubMed, FASEB J) - "Dietary management, sapropterin dihydrochloride, and pegvaliase are the current therapies; however, their limited efficacy and adverse effects highlight the pressing need for pharmacological treatments that restore PAH activity...Biological validation in R252Q mutant cells demonstrated significant upregulation of PAH and key tetrahydrobiopterin (BH4) pathway genes, including quinonoid dihydropteridine reductase (QDPR), sepiapterin reductase (SPR), and 6-pyruvoyl-tetrahydropterin synthase (PTS), following Pyr-TZ-2O treatment. Consistent with these findings, sandwich ELISA revealed a dose-dependent increase in PAH protein abundance post-Pyr-TZ-2O treatment. Conclusively, Pyr-TZ-2O can be considered a potential pharmacological chaperone capable of stabilizing mutant PAH and enhancing cofactor regeneration, offering a rational therapeutic approach for PKU."

Journal • Metabolic Disorders • Phenylketonuria • Rare Diseases

Geogenetic Stratification Correlates with Anthropometric Outcomes in a Mediterranean Cohort with PAH Deficiency (SSIEM 2026) - "Eighteen percent of the cohort is currently on pharmacological therapy (Sapropterin or Pegvaliase)... Our study reveals that the nutritional burden of PKU is not uniform. The Inland cluster faces a double challenge: a severe genetic phenotype and an increased risk of metabolic and anthropometric complications (e.g., higher BMI). Conversely, the Mediterranean Coastal cluster demonstrates a natural resilience thanks to milder mutations."

Metabolic Disorders • Phenylketonuria

Long-term evaluation of quality of life in patients with Phenylketonuria treated with Pegvaliase (SSIEM 2026) - "Pegvaliase treatment was effective in reducing Phe levels and achieving diet liberalization, thereby improving quality of life in PKU patients with historically poor dietary adherence. Despite initial treatment challenges, the therapy enabled substantial improvements in quality of life and dietary freedom."

Clinical • HEOR • Metabolic Disorders • Mood Disorders • Phenylketonuria • Rare Diseases

Management of Anaphylaxis during Pegvaliase Therapy in Adults with Phenylketonuria (SSIEM 2026) - "One patient developed grade 1 anaphylaxis during the escalation phase, while two developed anaphylaxis during maintenance therapy; one of these had recurrent episodes. Two patients required intramuscular adrenaline. In all three cases, pegvaliase was resumed soon after symptom resolution, with temporary dose reduction and/or additional premedication, including leukotriene receptor antagonists in one case."

Clinical • Immunology • Metabolic Disorders • Phenylketonuria • Rare Diseases

Gastrointestinal Symptoms Are Common in PKU But Under Recognised in Routine Care (SSIEM 2026) - "Sapropterin was used by 25% (n=97), sepiapterin by 4% (n=14), and one respondent used pegvaliase... GI symptoms were common across all ages in PKU, with many individuals experiencing persistent or moderate–severe symptoms that substantially affect daily life. A significant proportion required long-term medication or clinical investigation, and protein substitutes may contribute to symptom burden. Routine assessment of GI health should be embedded within PKU care pathways, and dietary management optimised to reduce symptoms and improve quality of life."

Constipation • Gastroenterology • Gastrointestinal Disorder • Metabolic Disorders • Phenylketonuria • Rare Diseases

Phenylalanine Reduction, LNAA Profiles, and Fat-Free Mass in Adults with PKU on Pegvaliase (SSIEM 2026) - "The unique responsiveness of tryptophan warrants further investigation, given its relevance to brain function. These findings suggest that dietary protein intake is a key determinant of lean mass preservation, even in hypophenylalaninemia."

Clinical • Metabolic Disorders • Phenylketonuria • Rare Diseases

Clinical outcomes in an adult with classic phenylketonuria treated with sepiapterin: first Italian real-life experience (SSIEM 2026) - " A female with classic PKU diagnosed via newborn screening (heterozygous c.194T>C and c.473G>A; 50% tetrahydrobiopterin [BH4]-responsive) was followed longitudinally...In 2022, pegvaliase treatment was initiated and then withdrawn after 2 months of dose-titration owing to an IgE mediated adverse event... In this first Italian real-world experience, sepiapterin enabled rapid metabolic control and increased protein intake in an adult patient with difficult-to-treat PKU and prior treatment failure. These findings support sepiapterin as a promising and well-tolerated treatment with the potential to improve PKU management and quality of life."

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

Efficacy and safety of pegvaliase in adolescents with phenylketonuria: interim results from PEGASUS part 2 (SSIEM 2026) - P3 | "These interim results from PEGASUS demonstrate that pegvaliase may effectively control blood Phe and enable dietary liberalization, including attainment of unrestricted diet, for adolescents with PKU, with a safety profile consistent with prior adult data."

Clinical • Metabolic Disorders • Musculoskeletal Pain • Phenylketonuria • Rare Diseases

Humanistic burden and unmet needs of patients with phenylketonuria (PKU): a US physician-reported survey perspective (SSIEM 2026) - "Patients received appropriate care: 91% prescribed low-Phe diet, 71% managed pharmacologically (29 on sapropterin, 8 pegvaliase, 9 sepiapterin)...Discussion. The burden of PKU and unmet treatment needs remain high in general and among patients with classical PKU."

Clinical • Metabolic Disorders • Mood Disorders • Phenylketonuria • Rare Diseases

Maternal PKU in the Post-MPKUCS Era: Reproductive Outcomes from the PHEFREE Rare-Disease Consortium for Phenylketonuria (SSIEM 2026) - "No women were on pegvaliase during pregnancy... Four decades after the Maternal Phenylketonuria Collaborative Study (MPKUCS) adverse pregnancy outcomes continue but at a substantially lower frequency. In this cohort 6% of offspring had CHD vs 14% in MPKUCS. Microcephaly in offspring to mothers with classic PKU prior to the MPKUCS occurred in 73%, and 23% with the MPKUCS intervention."

Cervical Cancer • Developmental Disorders • Endometriosis • Erectile Dysfunction • Gynecology • Infertility • Metabolic Disorders • Phenylketonuria • Polyendocrine Metabolic Ovarian Syndrome • Rare Diseases • Sexual Disorders • Uterine Leiomyoma • Women's Health

Successful Preconception Use of Pegvaliase with Classical Phenylketonuria Followed by Dietary Management During Pregnancy (SSIEM 2026) - "A 29-year-old woman with classical PKU who was well managed until puberty but exhibited persistent hyperphenylalaninemia due to poor dietary adherence from high school age. Following initiation of pegvaliase therapy, her blood Phe levels decreased to within the target range and remained stable, enabling preparation for pregnancy. After undergoing assisted reproductive treatment, she successfully conceived."

Metabolic Disorders • Phenylketonuria • Rare Diseases

Eating disorders and disordered eating in PKU: a systematic review (SSIEM 2026) - "Inclusion criteria comprised: patients early diagnosed, treated with a Phe-restricted diet at least until adolescence, +/- sapropterin/pegvaliase; not pregnant/lactating...They may misclassify treatment-related behaviours as pathological or, fail to detect PKU-specific patterns of concern. Purpose-designed screening instruments would support clinicians in initiating open, routine conversations about eating behaviour, food attitudes and the psychosocial burden of dietary management, enabling timely identification of individuals requiring assessment or referral to specialist ED services."

Review • Anorexia • Bulimia • CNS Disorders • Metabolic Disorders • Phenylketonuria • Rare Diseases

Improved global outcomes in two individuals with PAH deficiency following pegvaliase treatment. (SSIEM 2026) - "Shawn E. Christ has received consulting fees from BioMarin, Jnana/Otsuka, and PTC; and BioMarin has funded past and current research. Cary O. Harding has received consulting fees from BioMarin, Jnana, PTC, Sanofi, Pfizer, Synlogic, Tessera Therapeutics, and Tome Biosciences and conducted clinical research trials for BioMarin, Jnana, Sanofi, and Synlogic related to treatment of PAH deficiency"

Clinical • Metabolic Disorders • Phenylketonuria • Rare Diseases

Evaluation of CDX-6114, an Acid-Stable Oral Phenylalanine Ammonia Lyase, in a Porcine Model of PKU (SSIEM 2026) - "Current pharmacological interventions include chaperonins, large neutral amino acids, and injectable pegvaliase. These data support CDX-6114 as a viable oral enzyme substitution candidate for treatment of PKU. Future research will focus on long-term efficacy utilizing optimized pharmaceutical formulations."

Preclinical • Metabolic Disorders • Phenylketonuria • Rare Diseases • Targeted Protein Degradation

Phenylketonuria in Saudi Arabia: An Overview of Diagnosis, Genetics, and Therapeutic Strategies. (PubMed, Biology (Basel)) - "We outline established and emerging therapies, including dietary management, sapropterin (BH4), pegvaliase, large neutral amino acids, and investigational gene and mRNA therapies. Throughout, we identify where genuine Saudi-specific evidence exists and where general PKU knowledge is extrapolated to the Saudi context because of limited local data, most notably the absence of a national PKU registry. This review is intended to serve as a translational reference for clinicians, metabolic dietitians, geneticists, and policymakers engaged in PKU care in Saudi Arabia and the wider Arab region."

Journal • Review • Developmental Disorders • Gene Therapies • Mental Retardation • Metabolic Disorders • Pediatrics • Phenylketonuria • Rare Diseases

Nutritional and Metabolic Management of Phenylketonuria: Integrating Dietary Strategies, Medical Nutrition Therapy, and Emerging Treatments. (PubMed, Clin Nutr ESPEN) - "Effective management of PKU requires a multidisciplinary and personalized approach integrating nutritional, pharmacological, and emerging molecular therapies. While dietary management continues to be fundamental, novel therapeutic strategies may significantly improve long-term outcomes and quality of life in individuals with PKU."

Journal • Review • Gene Therapies • Metabolic Disorders • Phenylketonuria • Rare Diseases

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

Enrollment open • Immune Modulation • Immunology • Metabolic Disorders • Phenylketonuria • Rare Diseases

Re: Pegvaliase Treatment for Adolescents With Phenylketonuria: A Multi-Site Study. (PubMed, JIMD Rep) - No abstract available

Journal • Metabolic Disorders • Phenylketonuria • Rare Diseases

Quality of life after diet liberalization in individuals with phenylketonuria treated with Pegvaliase. (PubMed, Mol Genet Metab Rep) - "Pegvaliase treatment was effective in reducing blood Phe levels and achieving diet liberalization, thereby improving quality of life in individuals with PKU who historically had poor dietary adherence. Despite initial treatment challenges, the therapy enabled substantial improvements in quality of life and dietary freedom."

HEOR • Journal • Metabolic Disorders • Mood Disorders • Phenylketonuria • Psychiatry • Rare Diseases

Sepiapterin: A Distinct, Dual Mechanism of Action that Leads to Potential Treatment Benefits Across the Spectrum of Phenylketonuria Disease Severities. (PubMed, Adv Ther) - "In PKU, the PAH enzyme has reduced affinity for its substrate [phenylalanine (Phe)] or cofactor [tetrahydrobiopterin (BH4)], shows decreased substrate activation or becomes destabilized owing to protein misfolding...Until recently, only two pharmacological therapies were approved for PKU: sapropterin and pegvaliase; however, the need for additional treatment options remained...On the basis of its dual mechanism of action and favorable safety and tolerability profile, sepiapterin has the potential to treat a broad range of individuals with PKU across the spectrum of disease severities and ages. Thus, all individuals should be considered for an initial treatment trial with sepiapterin to establish responsiveness, regardless of genetic variant or phenotypic severity."

Journal • Metabolic Disorders • Phenylketonuria • Rare Diseases