Daybue (trofinetide) / Neuren, Acadia Pharma - LARVOL DELTA

Epilepsy Rates Among Individuals with Rett Syndrome Treated with Trofinetide versus Untreated in the United States (AES 2025) - "In this real-world analysis of RTT individuals, the TROF vs. NO-TROF groups exhibited similar rates of epilepsy during the 12-month post-index period. Among individuals with post-index epilepsy, there were similar rates of pre-index epilepsy across both groups."

Clinical • Late-breaking abstract • CNS Disorders • Developmental Disorders • Epilepsy • Mood Disorders • Movement Disorders • Vascular Neurology

Demographic and Clinical Characteristics among Adult Individuals with Rett Syndrome Treated with Trofinetide vs Untreated (AES 2025) - "Data on adult RTT individuals >20 years is scarce, especially for those initiating TROF. In this real-world analysis, only 16% of eligible adult RTT individuals were initiated on TROF, while 84% remain untreated. After matching, the treated group had higher rates of baseline comorbidities; potentially suggesting individuals with higher severity initiate TROF."

Clinical • Late-breaking abstract • CNS Disorders • Developmental Disorders • Epilepsy • Gastrointestinal Disorder • Mood Disorders • Movement Disorders • Vascular Neurology

Compatibility of Trofinetide with Ketogenic Diets in Patients with Rett Syndrome: Case Reports (AES 2025) - "In these anecdotal cases, patients with RTT treated with trofinetide were successfully started and maintained on ketogenic diets to further optimize seizure control. All patients achieved ketosis, as evidenced by optimal β-hydroxybutyrate levels, and all patients experienced improved seizure control."

Case report • Clinical • Late-breaking abstract • CNS Disorders • Developmental Disorders • Epilepsy • Movement Disorders • Psychiatry

Real-World Behavioral Improvements in Patients With Rett Syndrome Treated With Trofinetide: Interim Results of the LOTUS Study (AES 2025) - "The results of LOTUS show that caregivers observe the impact of trofinetide on meaningful functions and behaviors, such as nonverbal communication. The caregiver-reported behavioral improvements expand on the behavioral improvements observed in trofinetide clinical trials."

Clinical • Late-breaking abstract • Real-world • Real-world evidence • CNS Disorders • Developmental Disorders • Movement Disorders • Psychiatry

An Evaluation of Real-World Effectiveness and Safety of Trofinetide in Patients with Rett Syndrome: A Retrospective Chart Review (AES 2025) - "This study provides valuable insights into the real-world use of trofinetide in patients with RTT, including its effectiveness, safety, and treatment patterns. These findings will help inform clinical decision-making and optimize patient care in routine practice."

Late-breaking abstract • Real-world • Real-world effectiveness • Real-world evidence • Retrospective data • Review • Developmental Disorders • Movement Disorders • Respiratory Diseases

Remarkable Seizure Reduction with Trofinetide in An Adult with Rett Syndrome (AES 2025) - "To our knowledge, this patient is the first reported case of an older individual with RTT with significant seizure reduction after starting trofinetide. This suggests that long-term use of trofinetide may result in sustained symptom improvement in older individuals and in people who were diagnosed later in life with RTT. Our patient had seizure recurrence when an attempt was made to reduce the dose of lacosamide."

Clinical • CNS Disorders • Constipation • Developmental Disorders • Epilepsy • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Movement Disorders • Nephrology • Psychiatry

Real-World Benefits and Tolerability of Trofinetide for the Treatment of Male Patients With Rett Syndrome: Interim Results of the LOTUS Study (AES 2025) - "The results of the 7 males with RTT included in this follow-up suggest that the real-world benefits and tolerability of trofinetide in males follow similar trends with the general population of LOTUS."

Clinical • Late-breaking abstract • Real-world • Real-world evidence • CNS Disorders • Developmental Disorders • Infectious Disease • Movement Disorders • Pneumonia • Psychiatry • Respiratory Diseases

Trofinetide Improves Cognitive Function in APP/PS1 Mice by Suppressing Inflammation and Apoptosis. (PubMed, Mol Neurobiol) - "Mechanistically, trofinetide upregulated PPAR-γ, reduced BACE1, suppressed NF-κB phosphorylation, inhibited caspase-3 activation, and restored Bax/Bcl-2 balance, alleviating neuroinflammation and apoptosis. This study provides the first evidence that trofinetide improves cognitive function and mitigates Aβ pathology, neuroinflammation, and apoptosis in APP/PS1 mice and AβO-treated cells, highlighting its therapeutic potential for AD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • BCL2 • CASP3 • IGF1 • IL6 • TNFA

Real-World Treatment Patterns of Trofinetide in Rett Syndrome: Analysis of Medical Pharmacy-Linked Claims Database in the United States (ISPOR-EU 2025) - "TROF individuals who were persistent were on TROF for ≥14 months. Mean initial dose was lower in the persistent vs. non-persistent group."

Claims database • Clinical • HEOR • Real-world • Real-world evidence • Developmental Disorders • Movement Disorders

Record DAYBUE net sales of US$101.1 million in Q3 2025, up 11% from Q3 2024 (Neuren Pharma Press Release) - "Approximately 74% of the prescriptions to new patients in Q3 2025 were written by physicians in the community setting outside the Rett syndrome centers of excellence."

Sales • CNS Disorders • Developmental Disorders • Genetic Disorders

Genetics, Molecular Neuroscience, and Clinical Trials on the Path to the First FDA-Approved Treatment in Rett Syndrome (AACAP 2025) - "The intersection of genetic discovery, preclinical disease model evaluation, and natural history studies focused on clinical trial readiness enabled the identification and evaluation of novel therapies in RTT. The successful approval of trofinetide for the treatment of RTT provides evidence of the potential to develop new treatments for RTT as well as other neurodevelopmental disorders.GS, ND, RCT"

Clinical • CNS Disorders • Developmental Disorders • Epilepsy • Gene Therapies • Movement Disorders • Psychiatry • IGF1

Network-Medicine-Guided Drug Repurposing for Alzheimer's Disease: A Multi-Dimensional Systems Pharmacology Approach. (PubMed, Int J Mol Sci) - "Plerixafor emerged as the top-ranked small molecule (score: 1.170), while trofinetide achieved the highest peptide ranking (score: 1.387), though classified as speculative, pending AD-specific validation. Successful identification of the FDA-approved AD therapeutics memantine and donepezil among the top candidates validated the computational performance, while the predominance of mechanistic evidence classifications (86.7%) highlighted that network predictions represent hypothesis-generating tools requiring systematic experimental validation rather than definitive therapeutic recommendations. The framework bridges computational predictions with pharmaceutical development requirements, providing actionable prioritization for systematic preclinical investigation addressing AD intervention."

Journal • Alzheimer's Disease • CNS Disorders

Integrating plasma proteomics and genome-wide association data to identify therapeutic targets for retinal neurodegenerative diseases in Europeans. (PubMed, Int J Ophthalmol) - "This study identified six potential protein targets for RND and five existing drugs with therapeutic potential. By integrating plasma proteomics with genetic data, it provides a cost-effective framework for drug discovery."

Journal • Age-related Macular Degeneration • CNS Disorders • Diabetic Retinopathy • Glaucoma • Macular Degeneration • Ophthalmology • Retinal Disorders • BRD2 • ICAM1 • SVEP1

Real-world benefits and tolerability of trofinetide for the treatment of Rett syndrome: The LOTUS study. (PubMed, Dev Med Child Neurol) - No abstract available

Journal • Real-world evidence • Developmental Disorders • Movement Disorders

Automated analysis of facial dynamics in newborns: a path to earlier diagnosis of Rett syndrome (ECNP 2025) - "We plan to develop a framework capable of identifying newborns with suspected RTT before the onset of overt symptoms, by analyzing atypical facial dynamics captured in amateur videos. This tool could eventually be translated into a user-friendly application for the automated detection of suspected medical conditions using smartphone recordings. Such a system would support earlier referral to specialized centers, thereby accelerating diagnosis."

CNS Disorders • Movement Disorders

Study of trofinetide in Rett syndrome: Lessons from an approved drug for a severe neurodevelopmental disorder. (PubMed, Dev Med Child Neurol) - No abstract available

Journal • CNS Disorders • Developmental Disorders • Movement Disorders • Psychiatry

Real-world benefits and tolerability of trofinetide for the treatment of Rett syndrome: The LOTUS study. (PubMed, Dev Med Child Neurol) - "Results from the LOTUS study show improvements in the symptoms of RTT, with early insights into managing gastrointestinal symptoms in the context of real-world patient care."

Journal • Real-world evidence • Developmental Disorders • Movement Disorders

Safety Profiles of Trofinetide in Pediatric Rett Syndrome Population: A Real-World Postmarketing Pharmacovigilance Analysis. (PubMed, Clin Ther) - "This study provides critical real-world safety data on trofinetide use in pediatric Rett syndrome, identifying both expected and emerging AEs. Findings highlight the importance of monitoring dose-related and age-specific adverse events in clinical settings."

Adverse events • Journal • P4 data • Real-world evidence • CNS Disorders • Developmental Disorders • Dystonia • Epilepsy • Movement Disorders • Pediatrics • Psychiatry • Sleep Disorder

Genotype-Phenotype Correlation and Therapeutic Amenability in a Cohort of Rett Syndrome Patients: A Single-Center Study. (PubMed, Cureus) - "While no genotype-phenotype profile excludes treatment eligibility with Trofinetide, this correlation may inform early life response to treatment and eligibility for other emerging therapeutic options such as gene therapy. Early recognition, diagnosis, and treatment will certainly have an impact on patient outcomes."

Journal • CNS Disorders • Developmental Disorders • Epilepsy • Gene Therapies • Mental Retardation • Movement Disorders • Psychiatry

Cognitive Function in Rett Syndrome During Trofinetide Treatment (clinicaltrials.gov) - P=N/A | N=20 | Recruiting | Sponsor: University of Minnesota | Trial completion date: May 2025 ➔ Jun 2026 | Trial primary completion date: May 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Developmental Disorders • Movement Disorders

Real-world benefits and tolerability of trofinetide for the treatment of pediatric and adult patients with Rett Syndrom: the LOTUS study (CNSF 2025) - No abstract available

Clinical • Real-world • Real-world evidence • CNS Disorders

Real-world benefits and tolerability of trofinetide for the treatment of Rett Syndrom: interim analysis of the LOTUS study (CNSF 2025) - No abstract available

Clinical • Real-world • Real-world evidence • CNS Disorders

Assessing Minimal Clinically Important Difference Estimates for the Rett Syndrome Behavior Questionnaire (RSBQ) Using Data From the Trofinetide Clinical Program (ISPOR 2025) - No abstract available

Clinical • Developmental Disorders • Movement Disorders

Analysis of the Effect of Trofinetide Treatment on the Domain and Item-Level Responses of the Rett Syndrome Behavior Questionnaire Using Data From the LAVENDER Trial (ISPOR 2025) - P3 | "These analyses support trofinetide’s potential to improve Rett Syndrome across all 8 domains and 41 of the 45 items captured on the RSBQ. Similarly, NI were observed with trofinetide after accounting for floor and ceiling effects."

Developmental Disorders • Movement Disorders

Assessing Minimal Clinically Important Differenceestimates for the Rett Syndrome Behavior Questionnaire (RSBQ) using Data from the Trofinetide Clinical Program (ISPOR 2025) - P2, P3 | "These findings suggest that an estimated MCID for the RSBQ across the Trofinetide clinical trial program is likely to be within a 3- to 6-point difference. Changes in outcomes above this range are likely clinically important, based on natural variability observed in the data; smaller changes likely reflect measurement error rather than true clinical changes. These analyses should be confirmed via further investigation and expert consultation."

Clinical • Developmental Disorders • Movement Disorders