sapropterin / Generic mfg. - LARVOL DELTA

From dietary restriction to disease-targeted therapy: Sephience TM (sepiapterin) in phenylketonuria. (PubMed, Ann Med Surg (Lond)) - "Sepiapterin, a precursor of tetrahydrobiopterin (BH₄), enhances enzyme activity and stability, offering therapeutic benefit even in patients unresponsive to BH₄ alone. While careful monitoring for adverse effects such as gastrointestinal symptoms and hypophenylalaninemia is required, this approval represents a transformative step in precision medicine. Sephience has the potential to redefine the standard of care and improve long-term quality of life for individuals living with PKU."

Journal • Metabolic Disorders • Phenylketonuria • Rare Diseases

Evaluation of BH4 Responsiveness in Our PKU Patients (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Sohag University

New P1 trial • Metabolic Disorders • Phenylketonuria • Rare Diseases

A Single-Center Genotype-Phenotype Correlation Cohort Study of Hyperphenylalaninemia Patients: Genetic Analysis as a Deterministic Tool for Treatment Consistency. (PubMed, Mol Syndromol) - "Genomic DNA was obtained from 50 PKU, 2 tetrahydrobiopterin (BH4) deficiency, and 1 dihydropteridin reductase deficiency patients for next-generation sequencing of HPA-associated genes...This study implies that genetic testing is plausible in predicting pretreatment BH4 testing outcomes, aiding in decision-making before patient evaluation, and providing valuable guidance to metabolism specialists during HPA treatment. With more HPA genotypes analyzed and clinical data published, genotyping will hold a better deterministic position toward patient prognosis and therapeutic management."

Journal • Metabolic Disorders • Phenylketonuria • Rare Diseases • CDKN1A

Navigating Adolescence with PKU: Adherence, Metabolic Control, and Wellbeing in a UK Clinical Centre. (PubMed, Nutrients) - "Long term studies focusing on quality of life and neurocognition even when achieving the PKU European guidelines are necessary. Different therapeutic options are needed to improve the outcome of patients with PKU."

Journal • Retrospective data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Autism Spectrum Disorder • CNS Disorders • Depression • Genetic Disorders • Metabolic Disorders • Mood Disorders • Obesity • Phenylketonuria • Psychiatry • Rare Diseases • Suicidal Ideation

Modeling Intelligence Quotient (IQ) Changes Relative to Blood Phe Levels in Individuals With Phenylketonuria (PKU) Treated With Sepiapterin and Sapropterin Dihydrochloride (ISPOR-EU 2025) - "This model demonstrated that, compared to sapropterin, sepiapterin provided a greater reduction in blood Phe levels and consequently a lower probability of low IQ. These findings support the clinical relevance of effectively controlling blood Phe levels in PKU and highlight the value of sepiapterin in addressing the adverse cognitive outcomes that patients experience."

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

Epidemiology and Demographic Characteristics of Phenylketonuria in Brazil: A Real-World Data Study (2019-2024) (ISPOR-EU 2025) - "Although neonatal screening and dietary management are universally offered in Brazil, significant regional disparities remain in access to specialized care and pharmacotherapy, particularly in the North and Northeast. The low utilization of sapropterin highlights ongoing barriers to treatment. These findings underscore the need for targeted policy interventions and resource allocation to achieve equitable PKU care across the country."

Clinical • Real-world • Real-world evidence • 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

Change in quality of diet and burden of care in children with PKU treated with sapropterin dihydrochloride: a longitudinal study (SSIEM 2023) - No abstract available

Clinical • Longitudinal study • Observational data

Change in quality of diet and burden of care in children with PKU treated with sapropterin dihydrochloride: a longitudinal study (SSIEM 2023) - No abstract available

Clinical • Longitudinal study • Observational data

Change in quality of diet and burden of care in children with PKU treated with sapropterin dihydrochloride: a longitudinal study (SSIEM 2023) - No abstract available

Clinical • Longitudinal study • Observational data

A National Referral Clinic for Phenylketonuria (PKU) patients- treatment from a dietician`s point of view. (SSIEM 2023) - "Based on the large cohort established by the centralized care for PKU in Israel, we provide a large-scale information about patients with PKU in Israel who receive SAP treatment according to the classification of the disease, the frequency of the types of diets in which they are treated according to the classification of the disease, the patients` adherence to the nutritional treatment according to the type of recommended diet and our experience with reducing dietary restrictions for those treated with SAP."

Clinical • Metabolic Disorders • Phenylketonuria • Rare Diseases

Phase 3 APHENITY long-term study: Sepiapterin for treatment of phenylketonuria (SSIEM 2023) - P3 | "There is no cure; current treatments include dietary Phe restriction with amino acid supplementation, sapropterin (synthetic tetrahydrobiopterin [BH4], a key PAH cofactor), and phenylalanine ammonia lyase. Secondary endpoints are change from baseline in QOL (PKUQOL questionnaire, EuroQOL 5 Dimension), pharmacokinetics, and sepiapterin palatability/acceptability in children. It is anticipated that sepiapterin will be well tolerated and an increase in dietary Phe/protein consumption will be observed with daily administration of sepiapterin."

P3 data • Metabolic Disorders • Phenylketonuria • Psychiatry • Rare Diseases

A Large retrospective case series of managmnent of mothers with hyperphenylalaninaemia during pregnancy. (SSIEM 2023) - "We found that between our sites frequency of blood spot monitoring differed indicating that a standardisation of care in Hyperphe during pregnancy is required. A future collaborative, larger cohort data review on dietetic management, Phe levels, new-born screening and genetic testing would support the understanding and development of the best practice for this group of patients."

Retrospective data • Phenylketonuria

Change in quality of diet and burden of care in children with PKU treated with sapropterin dihydrochloride: a longitudinal study (SSIEM 2023) - "There were significant changes in food patterns, behaviors, and burden of care in children with PKU and their families after 6-months on sapropterin treatment. Appropriate patient education and support is essential when relaxing dietary management in PKU."

Clinical • Longitudinal study • Observational data • CNS Disorders • Depression • Metabolic Disorders • Mood Disorders • Pediatrics • Phenylketonuria • Psychiatry • Rare Diseases

Phase 3 APHENITY study: Oral sepiapterin for treatment of phenylketonuria (SSIEM 2023) - P3 | "There is no cure; current treatments include dietary Phe restriction with amino acid supplementation, sapropterin (synthetic tetrahydrobiopterin [BH4], a key PAH cofactor), and phenylalanine ammonia lyase. Secondary endpoints are % of subjects with baseline Phe levels ≥600 μmol/L who reach levels 600 μmol/L at the end of study, PK, and safety. This study was designed to support registration of sepiapterin for PKU and it is anticipated that a greater reduction in blood Phe will be observed after treatment with sepiapterin vs. placebo."

P3 data • Metabolic Disorders • Phenylketonuria • Psychiatry • Rare Diseases

Effects of Sapropterin against Non-Alcoholic Fatty Liver Disease in mice. (PubMed, Immunol Invest) - "Tetrahydrobiopterin (BH₄) maintains nitric oxide synthase (NOS) coupling...Additionally, sapropterin facilitated macrophage polarization toward an anti-inflammatory M2 phenotype (Cd206, Arg1), while suppressing pro-inflammatory M1 markers (Cd86). These findings indicated that sapropterin improvedNAFLD by regulatinglipid metabolism, inflammation, and fibrosis."

Journal • Preclinical • Dyslipidemia • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • CD36 • CD86 • FASN • IL10 • IL1B • IL6 • MRC1 • PPARA • SCARB1 • TGFB1

Improving sapropterin administration efficacy in PKU: Clinical practice case studies. (PubMed, Mol Genet Metab Rep) - "It was unclear if the improvements observed were associated with twice daily sapropterin administration, attention to taking it with fat containing meals, swallowing the tablets intact, or a combination of these. Further research to monitor the efficacy and safety of administration change is necessary."

Journal • Metabolic Disorders • Phenylketonuria • Rare Diseases

Sapropterin Dihydrochloride Responsiveness in Phenylketonuria: A Case Series Exploring Gaps in Comprehensive Patient Monitoring. (PubMed, Nutrients) - "Sapropterin dihydrochloride, a synthetic form of tetrahydrobiopterin (BH4), can enhance residual PAH activity, lowering blood Phe levels and increasing dietary tolerance in responsive patients... Sapropterin dihydrochloride effectively identified responders and improved dietary flexibility even with lower dosing protocols. Greater adherence to international standards, particularly regarding long-term neuropsychological monitoring, is needed to optimize patient care."

Journal • Retrospective data • Metabolic Disorders • Phenylketonuria • Psychiatry • Rare Diseases

Exercise and NO in HFrEF (clinicaltrials.gov) - P1 | N=68 | Completed | Sponsor: VA Office of Research and Development | Recruiting ➔ Completed | N=140 ➔ 68 | Trial completion date: May 2026 ➔ Jul 2025

Enrollment change • Trial completion • Trial completion date • Cardiovascular • Congestive Heart Failure • Heart Failure

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

Personalized Genotype-Based Approach for Treatment of Phenylketonuria. (PubMed, J Inherit Metab Dis) - "To further support personalized treatment strategies, we revised our publicly accessible PAH genotype & activity landscapes database to share the latest insights into PAH function and patient phenotypes-namely residual enzyme activity and responsiveness to sapropterin as conveyed by two alleles. This resource underscores the translational significance of functional research in PKU and offers a practical tool to support personalized treatment in clinical settings."

Journal • Metabolic Disorders • Phenylketonuria • Rare Diseases

Genomic profiling, implications for genotype-based treatment of 131 patients with phenylketonuria and characterization of novel p.Pro416Leu PAH variant. (PubMed, Sci Rep) - "We categorized all detected PAH genotypes accordingly and with 39.1% responsive and 44.5% probably responsive found that majority of patients may respond to BH4 therapy. Our study brings the updated spectrum of molecular genetic data, variant classification, characterization of novel p.Pro416Leu variant, detailed phenotypic characteristics and BH4 responsiveness for PKU patients from Serbia, therefore contributing to better understanding of molecular landscape of PKU."

Journal • Metabolic Disorders • Phenylketonuria • Rare Diseases

The Influence of Phenylalanine Fluctuations and Intake on a 24 h Sapropterin Responsiveness Test in Patients with Phenylketonuria. (PubMed, Children (Basel)) - "A 24 h sapropterin responsiveness test incorporating correction for natural fluctuations in PHE levels identified a proportion of sapropterin-responsive patients with mild PKU similar to that described in the literature. PHE consumption should be objectively controlled during the protocol to avoid bias in determining responsiveness."

Journal • Metabolic Disorders • Phenylketonuria • Rare Diseases