Treatment with trofinetide shows benefit compared to placebo for the ability to communicate in individuals with Rett syndrome: a secondary analysis of the LAVENDER study
Jeffrey Neul1, Alan Percy2, Timothy Benke3, Elizabeth Berry-Kravis4, Daniel Glaze5, Sarika U Peters1, Eric Marsh6, Di An7, Kathie Bishop7, James Youakim8
1Vanderbilt Kennedy Center, Vanderbilt University Medical Center, 2University of Alabama at Birmingham, 3Children’s Hospital of Colorado/University of Colorado School of Medicine, 4Rush University Medical Center, 5Texas Children’s Hospital/Baylor College of Medicine, 6Children's Hospital of Philadelphia, 7Acadia Pharmaceuticals Inc., 8Acadia Pharmaceuticals, Inc.
Objective:
To report communication-related endpoints from the phase 3 LAVENDER study in Rett syndrome (RTT).
Background:
RTT is a debilitating genetic neurodevelopmental disorder that primarily affects females and lacks an approved treatment. Loss of spoken language is a core feature, and most individuals also have a limited ability to communicate nonverbally. Trofinetide (n=93) demonstrated a clinical benefit over placebo (n=94) on global RTT-related co-primary endpoints in LAVENDER and was generally well tolerated.
Design/Methods:
Females with RTT, aged 5–20 years, were randomized 1:1 to trofinetide or placebo for 12 weeks. Secondary efficacy endpoints related to verbal and non-verbal communication were adapted for RTT or developed for this study, including the caregiver-rated Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist-Social (CSBS-DP-IT Social) Composite score (key secondary endpoint; scored 0-26, higher score indicating better ability to communicate) and the novel RTT-specific clinician rating scales (0 [normal] to 7 [severe impairment]) that measure the ability to communicate choices to assess the practical ability to communicate nonverbally (RTT-Clinician Rating of Ability to Communicate Choices [RTT-COMC]) and verbally (RTT- Clinician Rating of Verbal Communication [RTT-VCOM]).
Results:
Based on the change from baseline at Week 12, trofinetide demonstrated a statistically significant difference versus placebo for the CSBS-DP-IT Social Composite score (mean [SE] -0.1 [0.28] versus -1.1 [0.28]; least squares mean [LSM] difference 1.0; 95% CI: 0.3–1.7; p=0.0064; Cohen’s d effect size, 0.43), and nominally significant difference for RTT-COMC (mean [SE] -0.4 [0.12] versus 0.0 [0.10]; LSM difference -0.3; 95% CI: -0.6–0.0; p=0.0257; Cohen’s d effect size, 0.36). As expected, no difference was observed for the RTT-VCOM.
Conclusions:
In the LAVENDER study, differences for trofinetide versus placebo were observed in scales measuring ability to communicate. The communication scales used in this study may be useful in future trials for RTT and other neurodevelopmental disorders.