Neuropediatrics 2025; 56(S 01): S1-S24
DOI: 10.1055/s-0045-1812161
Varia

Efficacy and Safety of Trofinetide for the Treatment of Rett Syndrome: Results from the Pivotal Phase 3 LAVENDER Study

Authors

  • A. Huber

    1   Acadia Pharmaceuticals GmbH, Medical Affairs, Basel, Switzerland

  • J. Neul

    2   Vanderbilt Kennedy Center, Nashville, Tennessee, United States

  • A. Percy

    3   University of Alabama at Birmingham, Birmingham, Alabama, United States

  • T. Benke

    4   Children's Hospital of Colorado, Aurora, Colorado, United States

  • E. Berry-Kravis

    5   Rush University Medical Center, Chicago, Illinois, United States

  • D. Glaze

    6   Texas Children's Hospital, Houston, United States

  • E. Marsh

    7   Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

  • K. Bishop

    8   Acadia Pharmaceuticals, San Diego, California, United States

  • J. Youakim

    8   Acadia Pharmaceuticals, San Diego, California, United States
Further Information
Also available at
 
 

    Background/Purpose: Rett syndrome (RTT) is a debilitating genetic neurodevelopmental disorder primarily affecting females. Trofinetide is a synthetic analog of glycine–proline–glutamate, a naturally occurring tripeptide cleaved from insulin-like growth factor 1. Phase 2 studies in RTT demonstrated a clinical benefit over placebo in clinician- and caregiver-assessed efficacy measures. Here, we present the results of LAVENDER, a randomized, placebo-controlled, phase 3 study of trofinetide in girls and young women with RTT.

    Methods: Females with RTT, aged 5 to 20 years, were randomized 1:1 to twice-daily oral trofinetide or placebo for 12 weeks. Efficacy endpoints included the Rett Syndrome Behavior Questionnaire (RSBQ), a caregiver assessment of core RTT symptoms (co-primary), the Clinical Global Impression-Improvement (CGI-I) scale (co-primary), and the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist-Social (CSBS-DP-IT Social) composite score (key secondary).

    Results: Overall, 187 participants were randomized to trofinetide (n = 93) or placebo (n = 94). After 12 weeks of treatment, trofinetide demonstrated a statistically significant improvement over placebo for co-primary and key secondary endpoints. Least squares (LS) mean change from baseline to week 12 in the RSBQ for trofinetide versus placebo was −4.9 versus −1.7 (p = 0.0175; Cohen's d effect size = 0.37), LS mean CGI-I score at week 12 was 3.5 versus 3.8 (p = 0.0030; Cohens’ d effect size = 0.47), and LS mean change from baseline to week 12 in the CSBS-DP-IT Social composite score was −0.1 versus −1.1 (p = 0.0064; Cohen's d effect size = 0.43). Serious adverse events were reported in 3.2% of participants in the trofinetide and placebo groups. The most common adverse event in the trofinetide and placebo groups was diarrhea (80.6 and 19.1%, respectively), with 98% of all cases experiencing mild-to moderate severity.

    Conclusion: This study demonstrated that trofinetide is efficacious and has an acceptable safety profile in females with RTT.


     

    No conflict of interest has been declared by the author(s).

    Publication History

    Article published online:
    26 September 2025

    © 2025. Thieme. All rights reserved.

    Georg Thieme Verlag KG
    Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany