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

Rett syndrome: MECP2 biology, multisystem pathophysiology, and the evolving therapeutic landscape. (PubMed, Eur J Pediatr) - "RTT is a multisystem monogenic disorder whose management is shifting from symptom control toward disease modification. Phenotypic rescue after MECP2 restoration in rodent models provides the rationale for this shift but does not establish that RTT is reversible in patients; progress now depends on validated biomarkers, dose-controlled disease-modifying therapies, long-term outcome data, and equitable global access."

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

Rett syndrome in the therapeutic era: Rethinking diagnosis, boundaries, clinical outcomes, and financing. (PubMed, Dev Med Child Neurol) - "These have led to the first drug approved for core symptoms of a neurodevelopmental disorder, trofinetide, and gene replacement programs at advanced development...These include diagnosis before developmental regression and of individuals without core RTT features, including males; the role of MECP2 testing in RTT diagnosis; the boundaries of RTT; instruments needed for assessing clinical evolution in research and practice; the definition of meaningful clinical improvement; and the development, availability, and affordability of new treatments. These topics are reviewed in terms of their implications for RTT and for other genetic neurodevelopmental disorders."

Clinical data • Financing • Journal • Review • CNS Disorders • Developmental Disorders • Movement Disorders • Psychiatry

Remarkable seizure reduction with trofinetide treatment in an adult with Rett syndrome: A case report. (PubMed, Seizure) - No abstract available

Journal • CNS Disorders • Developmental Disorders • Epilepsy • Movement Disorders

European Commission Approves DAYBU (trofinetide) as the First and Only Treatment for Neurobehavioral Symptoms of Rett Syndrome in the European Union (Yahoo Finance)

EMA approval • Developmental Disorders • Movement Disorders

Characteristics of adult individuals with Rett syndrome treated or untreated with trofinetide in the United States. (PubMed, Front Neurol) - "There is a high unmet need for adult individuals with RTT to initiate treatment with TROF. Treated group had higher rates of RTT related clinical features and differential diagnoses; however, the observation that TROF is being used in adults with greater to similar baseline complexity compared to untreated may provide reassurance for prescribers to consider TROF in adults who were untreated."

Journal • CNS Disorders • Developmental Disorders • Mood Disorders • Movement Disorders • Psychiatry • Vascular Neurology

Expert Consensus on Real-World Use of Trofinetide for Rett Syndrome Using a Modified Delphi Method. (PubMed, Ann Child Neurol Soc) - "While side effects can emerge with trofinetide, they are manageable in most cases. Recommendations highlight a flexible, patient-centered approach to trofinetide use to optimize efficacy while addressing tolerability challenges and supporting adherence."

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

Acadia Pharmaceuticals Reports Second Quarter 2026 Financial Results (Businesswire) - "GAAP net product sales of NUPLAZID were $183 million for the second quarter of 2026, up 9% compared to GAAP net product sales of $168 million for the second quarter of 2025, and up 10% as compared to non-GAAP adjusted net product sales of $166 million for the second quarter of 2025. Net product sales of DAYBUE were $125 million for the second quarter of 2026, an increase of 30% as compared to $96 million for the second quarter of 2025."

Sales • CNS Disorders • Genetic Disorders • Parkinson's Disease • Rare Diseases

Mapping Trofinetide Polypharmacology in Rett Syndrome: A Multi-Stage Computational Analysis. (PubMed, J Comput Chem) - "In different targets, the proline fragment frequently contributes to hydrophobic anchoring. Taken together, these results provide testable structural hypotheses for the multi-target interaction of trofinetide in RTT and a computational framework to guide experimental validation and next-generation multi-target design."

Journal • CNS Disorders • Developmental Disorders • Movement Disorders • Psychiatry • CHRM1 • GSK3B

Adapting a Psychosocial Support Intervention for the Rett Syndrome Community (clinicaltrials.gov) - P=N/A | N=60 | Not yet recruiting | Sponsor: Colorado State University

New trial • Developmental Disorders • Movement Disorders

Trofinetide Use and Treatment Patterns Among Children Aged 2-4 Years with Rett Syndrome in the United States: A Retrospective Specialty Pharmacy Linked Claims Database Analysis. (PubMed, Int J Gen Med) - "Non-persistent children had significantly higher baseline rates of dysphagia, gastrostomy, and breathing irregularities, suggesting that early disease-related multisystem complications may be associated with reduced treatment continuity. These findings complement DAFFODIL and provide early real-world evidence on TROF persistence, restarts, and dosing patterns in this young RTT population."

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

Real-World Demographics, Clinical Characteristics, and Predictors of Persistence Among Males with Rett Syndrome Treated with Trofinetide. (PubMed, Adv Ther) - "Most males with RTT remained untreated during this study period, while TROF initiation appeared concentrated among those with greater pre-index concomitant comorbidities and neurology involvement. Persistence beyond 6 months was common, supporting continued long-term use of TROF in males with RTT in real-world practice."

Journal • Real-world evidence • CNS Disorders • Developmental Disorders • Epilepsy • Movement Disorders • Psychiatry • Respiratory Diseases

Acadia Pharmaceuticals…announced that…the CHMP of the European Medicines Agency (EMA) has adopted a positive opinion following a re-examination procedure, recommending the granting of a marketing authorization for DAYBU (trofinetide) for the treatment of neurobehavioral symptoms of Rett syndrome in adults and pediatric patients aged five years and older (Businesswire) - "If granted marketing authorization by the European Commission, DAYBU would be the first therapy approved for this indication in the European Union (EU)....The CHMP’s recommendation is primarily based on results from the Phase 3 LAVENDER study, which demonstrated statistically significant and clinically meaningful improvements in core features of Rett syndrome....Following the CHMP recommendation, the European Commission will review the opinion and is expected to issue a final decision in the coming months."

CHMP • CNS Disorders • Rare Diseases

Cognitive Function in Rett Syndrome During Trofinetide Treatment (clinicaltrials.gov) - P=N/A | N=20 | Recruiting | Sponsor: University of Minnesota | Trial completion date: Jun 2026 ➔ Jun 2027 | Trial primary completion date: Jun 2026 ➔ Jun 2027

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

Real-World Treatment Landscape of Individuals with Rett Syndrome Treated and Untreated with Trofinetide in the United States. (PubMed, J Health Econ Outcomes Res) - "TROF uptake appeared concentrated in younger, specialist-managed individuals with more clearly documented RTT-related features, while three-quarters remained untreated. These findings highlight the need to better understand treatment pathways and barriers to initiation in males and adults in routine RTT care."

HEOR • Journal • Real-world evidence • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Genetic Disorders • Mood Disorders • Movement Disorders • Pediatrics • Vascular Neurology

Rett syndrome and real-world treatment patterns of trofinetide in the United States. (PubMed, J Med Econ) - "Stable dosing patterns were observed among persistent individuals, while greater dose variability was observed among non-persistent individuals. Thus, these findings may provide guidance to clinicians about long-term TROF use in real-world practice."

HEOR • Journal • Real-world evidence • Developmental Disorders • Infectious Disease • Movement Disorders

Drug-induced gastric motility disorders: A disproportionality analysis from the FAERS and CVARD databases. (PubMed, PLoS One) - "This study identifies a broad spectrum of drug-associated gastric motility disorders with distinct temporal profiles. These findings provide evidence-based priorities for enhanced pharmacovigilance and inform clinical decision-making to mitigate this preventable cause of morbidity."

Journal • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder

Toward an NGF-based therapy for Rett syndrome. (PubMed, Front Neurosci) - "Although recent therapeutic advances, such as the approval of Trofinetide, offer partial relief, no comprehensive curative treatment is currently available...The use of intranasal delivery further enhances translational potential by overcoming blood-brain barrier limitations. Together, these studies provide a strong rationale for pursuing NGF-based therapies in RTT and encourage further investigations to optimize dosing, timing, and safety in preclinical and clinical settings."

Journal • Review • CNS Disorders • Developmental Disorders • Inflammation • Movement Disorders • Pain • Psychiatry

Clinical experience using trofinetide in Rett syndrome and related MECP2 diagnosis at the children's hospital of Philadelphia post approval. (PubMed, Front Neurol) - "The data highlights the need for further work to determine long-term benefits in the full spectrum of MECP2 related disorders. Finally, the study highlights the importance of titration, individualized dosing and side effect management to improve retention and outcomes."

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

Hydrophobic Tag-Assisted Scalable Synthesis of Trofinetide and Its GPE Analogues. (PubMed, J Pept Sci) - "In addition to establishing a robust process for trofinetide, the strategy enabled synthesis of two novel non-natural GPE analogues, H-Gly-Aib-Glu-OH and H-Gly-Aib-Asp-OH. This tag-assisted LPPS provides a greener alternative to existing routes and offers a versatile platform for industrial production of short-chain oligopeptides."

Journal • Developmental Disorders • Movement Disorders

Impact of Real-World, Case-Driven CME Learning on Diagnostic and Therapeutic Practice in Rett Syndrome (AAN 2026) - "Background The approval of trofinetide, the first therapy for RTT, requires greater clinician preparedness in treatment selection, caregiver counseling, and team-based management...The overall educational effect size was large (Cohen’s d = 0.82), with 79% of participants self-reporting intended practice changes, most related to AE mitigation and enhanced team-based collaboration. Conclusions The initiative produced measurable gains in clinician knowledge, competence, and confidence in RTT care, supporting improved diagnostic and management practices."

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

Severe Hyperventilation Apnea Spells in Pitt Hopkins Syndrome and Beyond: A Remarkable Response to IV Diamox in the ICU (AAN 2026) - "These mice show reduced hyperventilation and improved behavior after administration of promyelinating drugs such as clemastine and sobetirome. Additionally, voltage gated sodium channel NaV1.8 has been shown to be abnormally expressed in the RTN in PTHS mouse models, suggesting that blockade of these channels may offer a therapeutic benefit. Lastly, other novel therapeutic options include vorinostat (chaperone for mRNA folding), trofinetide (IGF-1 analogue), MZ-1866 (recombinant AAV9 vector with TCF4 trasngene), and recurrent stem cell transplants."

Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Mental Retardation • Respiratory Diseases • Solid Tumor • IGF1 • NAV1 • TCF4

Real-world Benefits and Tolerability of Trofinetide for the Treatment of Adults with Rett Syndrome: the LOTUS Study (AAN 2026) - "The highest incidence of diarrhea was reported at week 2 of treatment (60.0%); most reports were contained inside the patient’s diaper. Conclusions The real-world benefits and tolerability of trofinetide in adults with RTT in LOTUS followed similar trends to the overall LOTUS population."

Clinical • Real-world • Real-world evidence • Constipation • Developmental Disorders • Movement Disorders

Insulin and Insulin-like Growth Factor 1 Signaling as a Modulator of MYC Expression in the Meibomian Gland. (PubMed, Biomedicines) - "Murine eyelids treated with an IIS agonist demonstrated a more mesenchymal phenotype and significantly induced MYC expression. Collectively, these results suggest that the IIS pathway may represent a novel approach for regulating high MYC expression in SebCA."

Journal • Eye Cancer • Oncology • Solid Tumor • IGF1 • IGF1R • IR • MYC

Design, synthesis and evaluation of trofinetide prodrug based on diketopiperazine strategy. (PubMed, Bioorg Med Chem) - "Compared to oral administration of trofinetide, subcutaneous injection of TFD 10 markedly prolonged the half-life (6-fold) and substantially increased systemic exposure (40-fold), successfully achieving the design objectives. This study validates the feasibility of this strategy, and TFD 10, as a proof-of-concept lead compound, demonstrates significant potential for further development."

Journal • Developmental Disorders • Movement Disorders • Pediatrics

Modulating alternative splicing of MECP2 is a potential therapeutic strategy for Rett syndrome. (PubMed, Sci Transl Med) - "The current US Food and Drug Administration-approved treatment for RTT, trofinetide, mildly alleviates some symptoms...Last, an exon 2-skipping morpholino up-regulated MeCP2-E1 in vivo in mice. These data set the stage for a potential therapeutic strategy using antisense oligonucleotides to promote isoform switching in patients with RTT who carry partially functioning alleles of MECP2."

Journal • CNS Disorders • Developmental Disorders • Movement Disorders