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

Disease-modifying therapies for Rett syndrome: a review for neurologists. (PubMed, Front Neurol) - "Until the recent approval of trofinetide, management relied exclusively on symptomatic treatment and multidisciplinary supportive care...TSHA-102 uses an intrathecally delivered miniMECP2 transgene regulated by a microRNA-based autoregulatory system, whereas NGN-401 delivers full-length MECP2 via intracerebroventricular administration using a synthetic expression-feedback circuit...Finally, we address key translational considerations such as optimal timing of intervention, dosing constraints, outcome measurement in severely impaired populations, long-term safety surveillance, and barriers to broad and equitable access. The RTT gene therapy experience serves as a model for precision medicine in other monogenic neurodevelopmental disorders, illustrating both the transformative promise and the substantial complexities of translating genetic science into meaningful clinical benefit."

Journal • Review • CNS Disorders • Developmental Disorders • Gene Therapies • Movement Disorders • Pediatrics • Psychiatry • ADAR

Acadia provides update on regulatory submission for trofinetide for the treatment of Rett syndrome in the European Union (Neuren Pharma Press Release) - "Neuren Pharmaceuticals (ASX: NEU) advised that its licensee Acadia Pharmaceuticals...has today provided an update on its marketing authorization application (MAA) for trofinetide for the treatment of Rett syndrome in the European Union (EU). Acadia was informed by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) of a negative trend vote on its MAA for trofinetide for the treatment of Rett syndrome, following its recent CHMP oral explanation. Subject to the outcome of the CHMP vote in February, Acadia intends to request a re-examination of the opinion by the CHMP upon its formal adoption."

CHMP • Genetic Disorders

Post-marketing safety concerns with trofinetide: a disproportionality analysis of the first therapeutic agent for Rett syndrome based on the FDA adverse event reporting system (FAERS). (PubMed, Front Pharmacol) - "This study unveils certain potential risks associated with trofinetide in real-world applications. Medical staffs should pay more attention to AEs of patients on the first month."

Adverse events • Journal • P4 data • Autism Spectrum Disorder • Developmental Disorders • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Infectious Disease • Influenza • Movement Disorders • Respiratory Diseases

Real-World Benefits and Tolerability of Trofinetide for the Treatment of Male Patients With Rett Syndrome: LOTUS Study Interim Results (ACMG 2026) - "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 • Real-world • Real-world evidence • CNS Disorders • Developmental Disorders • Infectious Disease • Movement Disorders • Pneumonia • Respiratory Diseases

Dual Diagnosis of Klinefelter Syndrome and Rett Syndrome in a Male Patient: A Rare Co-occurrence with Diagnostic and Phenotypic Implications (ACMG 2026) - "Treatment and Management This patient is a candidate for trofinetide, a treatment for Rett syndrome shown to provide subtle behavioral benefits...Genetic testing identified Klinefelter syndrome (47,XXY) and a pathogenic MECP2 variant (c.387-3C>G, p.?), confirming a dual diagnosis of Klinefelter and Rett syndromes. Because of his X-chromosome complement, we anticipate a disease course similar to that seen in females with classic Rett syndrome."

Clinical • Cardiovascular • CNS Disorders • Developmental Disorders • Endocrine Disorders • Genetic Disorders • Mental Retardation • Movement Disorders • Obstructive Sleep Apnea • Ophthalmology • Respiratory Diseases • Sleep Apnea • Sleep Disorder

858106: Advancements in Rett Syndrome (RTT) Care: Caregiver and Expert Panel Discussion (This activity is supported by Acadia Pharmaceuticals Inc.) (ACMG 2026) - "These sessions focus on highlighting new developments, generating interest in innovative products or services, and sharing the latest insights with meeting participants. These activities are not part of the official ACMG meeting programming and are not accredited by ACMG.Learning Objectives:• Review RTT diagnostic criteria and multisystem impact• Examine clinical trial data from LAVENDER, LILAC-1, and LILAC-2, and real-world observations from the LOTUS post approval study• Discover caregiver insights based on their experiences with RTT and DAYBUE"

CNS Disorders • Developmental Disorders • Movement Disorders

Trofinetide-Induced Enterocolitis Syndrome in a Child with Rett Syndrome. (PubMed, J Child Neurol) - "The concept of drug-induced enterocolitis syndrome (DIES) has been reported with other agents; however, to our knowledge, this represents the first reported case of FPIES/DIES triggered by trofinetide. This case expands the spectrum of trofinetide-related adverse reactions and emphasizes the need to distinguish immune-mediated enterocolitis from dose-dependent osmotic diarrhea and highlights the importance of clinician vigilance when initiating similar therapies in children with complex neurodevelopmental disorders."

Journal • CNS Disorders • Developmental Disorders • Gastrointestinal Disorder • Movement Disorders • Psychiatry

Neuren Pharmaceuticals…announced that its partner, Acadia Pharmaceuticals, has received US Food and Drug Administration (FDA) approval of DAYBUE STIX (trofinetide) for oral solution, a dye- and preservative-free powder formulation of trofinetide for the treatment of Rett syndrome in adult and pediatric patients two years of age and older (Neuren Pharma Press Release) - "The approval of this new formulation was informed by the results of a bioequivalence study, which demonstrated that both original DAYBUE (trofonetide) oral solution and the new DAYBUE STIX (trofinetide) for oral solution powder formulation provide comparable exposure....Acadia expects DAYBUE STIX to be available on a limited basis starting in the first quarter of 2026 and more broadly early in the second quarter of 2026."

FDA approval • Launch US • CNS Disorders • Developmental Disorders • Genetic Disorders

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