sapropterin / Generic mfg. - LARVOL DELTA

Two-Year Outcomes of Sapropterin Treatment in Children with Phenylketonuria: A Longitudinal Observational Study of Metabolic, Dietary, and Psychosocial Effects. (PubMed, Nutrients) - " Sapropterin enabled more flexible, sustainable dietary management in responsive children with PKU, supporting metabolic control, growth, and improved family well-being and social participation. Equitable access to therapies and long-term dietetic support remain essential to optimize outcomes."

Journal • Observational data • CNS Disorders • Depression • Metabolic Disorders • Phenylketonuria • Psychiatry • Rare 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

Impact of health-system specialty pharmacy utilization on sapropterin adherence in patients with phenylketonuria (PKU) (ACMG 2026) - "Sapropterin, a synthetic tetrahydrobiopterin cofactor that enhances residual PAH activity, is used to lower PHE levels in responsive patients and is dispensed exclusively through specialty pharmacies... There was no statistically significant difference in overall adherence among PKU patients receiving sapropterin from an integrated HSSP compared to a non-integrated specialty pharmacy when accounting for covariates. However, use of an integrated HSSP had higher likelihood of a high degree of adherence (PDC >90%) and generated substantial revenue. The neutral findings for the primary endpoint may reflect type II error due to low sample size."

Adherence • Clinical • Alzheimer's Disease • Cognitive Disorders • Genetic Disorders • Metabolic Disorders • Mood Disorders • Phenylketonuria • Rare Diseases

Age-Dependent Variation in Blood Biopterin Peaks Following Oral Tetrahydrobiopterin Administration in Phenylketonuria. (PubMed, J Inherit Metab Dis) - "These findings indicate that BH4 loading tests performed in infants and preschool-aged children (1 month-5 years)-in whom biopterin peaks tend to be low-or in patients with high baseline Phe levels may yield suppressed biopterin peaks and false-negative results. Reassessment of BH4 responsiveness and age-appropriate dose adjustment should be considered when necessary."

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

Efficacy and safety of sepiapterin versus sapropterin in patients with phenylketonuria: Results from the Phase 3, randomized, crossover, open-label, active-controlled AMPLIPHY trial. (PubMed, Metabolism) - "Sepiapterin was superior to the highest approved dose of sapropterin in lowering blood Phe. No new safety signals were observed. The trial was registered in the UK Clinical Study Registry, ISRCTN, on January 29, 2024 (ID number, ISRCTN79102999; https://www.isrctn.com/ISRCTN79102999)."

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

Enhancement of therapeutic transgene insertion for treatment of murine phenylketonuria. (PubMed, Mol Ther Nucleic Acids) - "Separately, we demonstrate that rare hepatocytes harboring transgene insertions were successfully expanded to a therapeutically relevant population through selection based upon resistance to acetaminophen toxicity, but this method was hampered by adverse effects upon AAV vector production and the neurologic function of treated neonatal mice related to the presence of shRNA sequences in the AAV vector. These results demonstrate that pharmacologic inhibition of alternative DNA repair pathways can significantly enhance HDR-mediated transgene insertion in vivo."

Journal • Preclinical • Gene Therapies • Genetic Disorders • Metabolic Disorders • Phenylketonuria • Rare Diseases

Neurological and psychiatric issues in 187 adults with early-treated PKU: The ECOPHEN study. (PubMed, Mol Genet Metab) - "The present study highlights neurological complications persisting despite early treatment, particularly in classic PKU. Diet adherence and current plasma Phe levels did not correlate significantly with neurological or psychiatric outcomes, possibly due to suboptimal metabolic control. Limitations included the cross-sectional design, absence of control group, and retrospective data collection. Overall, adults with early-treated PKU show a generally favorable outcome but remain at risk for neuropsychiatric manifestations, supporting the need for lifelong follow-up including neurologic and psychiatric evaluation."

Journal • CNS Disorders • Cognitive Disorders • Depression • Mental Retardation • Metabolic Disorders • Migraine • Mood Disorders • Movement Disorders • Otorhinolaryngology • Pain • Phenylketonuria • Psychiatry • Rare Diseases

Impact of health-system specialty pharmacy utilization on sapropterin adherence in patients with phenylketonuria (PKU) (ASHP 2025) - No abstract available

Adherence • Clinical • Metabolic Disorders • Phenylketonuria • Rare Diseases

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