Abstract Details

Title 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

Topic Child Neurology and Developmental Neurology

Presentation(s) P13 - Poster Session 13 (8:00 AM-9:00 AM)

Poster/Presentation
Number 4-006

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.

Authors/Disclosures
Alan K. Percy, MD, FAAN PRESENTER	Dr. Percy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia Pharmaceuticals. Dr. Percy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Taysha Gene Therapies. Dr. Percy has received personal compensation in the range of $0-$499 for serving as a Consultant for Neurogene. Dr. Percy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Taysha Gene Therapies. Dr. Percy has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for IOS Press.
Jeffrey Neul, MD, PhD (Vanderbilt University Medical Center)	Dr. Neul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Neul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GW Pharmaceuticals. Dr. Neul has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Signant Health. Dr. Neul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Analysis Group. Dr. Neul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Taysha Gene Therapies. Dr. Neul has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alcyone. Dr. Neul has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ovid. Dr. Neul has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Neul has stock in LizardBio. The institution of Dr. Neul has received research support from NIH. The institution of Dr. Neul has received research support from Acadia. The institution of Dr. Neul has received research support from GW Pharmaceuticals. The institution of Dr. Neul has received research support from International Rett Syndrome Foundation. The institution of Dr. Neul has received research support from Rett Syndrome Research Trust.
Timothy A. Benke, MD, PhD	The institution of Dr. Benke has received research support from NIH, RSRT, IRSF and Children's Hospital Colorado. The institution of Dr. Benke has received research support from Acadia, GW, RSRT, Ovid/Takeda, Marinus. The institution of Dr. Benke has received research support from Acadia, CUREGRI, GRINtherapeutics, GW, IRSF, Marinus, Neurogene, Taysha, Ultragenyx and Zogenix/UCB; .
Elizabeth M. Berry-Kravis, MD, PhD (Rush University Medical Center)	The institution of Dr. Berry-Kravis has received research support from NIH. The institution of Dr. Berry-Kravis has received research support from Ionis. The institution of Dr. Berry-Kravis has received research support from Zynerba. The institution of Dr. Berry-Kravis has received research support from Roche. The institution of Dr. Berry-Kravis has received research support from CDC. The institution of Dr. Berry-Kravis has received research support from FRAXA Research Foundation. The institution of Dr. Berry-Kravis has received research support from GeneTx. The institution of Dr. Berry-Kravis has received research support from Angelman Syndrome Foundation. The institution of Dr. Berry-Kravis has received research support from Acadia. The institution of Dr. Berry-Kravis has received research support from Ultragenyx. The institution of Dr. Berry-Kravis has received research support from Mallinckrodt. The institution of Dr. Berry-Kravis has received research support from Together Strong Foundation. The institution of Dr. Berry-Kravis has received research support from Zevra. The institution of Dr. Berry-Kravis has received research support from Taysha. The institution of Dr. Berry-Kravis has received research support from Tetra. The institution of Dr. Berry-Kravis has received research support from Neuren.
Daniel Glaze, MD (Baylor College of Medicine)	Dr. Glaze has nothing to disclose.
	No disclosure on file
Eric D. Marsh, MD, PhD (Children's Hospital of Philadlephia)	Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia Pharmacuticals. Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Stoke Therapeutics. Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia Pharmaceuticals. The institution of Dr. Marsh has received research support from NIH. The institution of Dr. Marsh has received research support from Rett Syndrome Research Trust. The institution of Dr. Marsh has received research support from International Rett Syndrome Foundation. The institution of Dr. Marsh has received research support from Eagles Autism Challenge. The institution of Dr. Marsh has received research support from LouLou Foundation. The institution of Dr. Marsh has received research support from International CDKL5 Resarch Foundation. The institution of Dr. Marsh has received research support from Acadia Pharmaceuticals. The institution of Dr. Marsh has received research support from Marinus. The institution of Dr. Marsh has received research support from Stoke Therapeutics. The institution of Dr. Marsh has received research support from Takeda Pharmaceuticals. Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving as a Grant Review with NIH. Dr. Marsh has received personal compensation in the range of $5,000-$9,999 for serving as a Expert Witness with Department of Human Services. Dr. Marsh has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Medscape.
Di Di An	No disclosure on file
Kathie M. Bishop, PhD	Dr. Bishop has received personal compensation for serving as an employee of Acadia Pharmaceuticals, Inc. . Dr. Bishop has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for DTx Pharma. Dr. Bishop has stock in Acadia Pharmaceuticals, Inc..
James M. Youakim, MD (Acadia Pharmaceuticals)	Dr. Youakim has received personal compensation for serving as an employee of Acadia Pharmaceuticals. Dr. Youakim has stock in Acadia Pharmaceuticals.

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