Real-World Behavioral Improvements in Patients With Rett Syndrome Treated With Trofinetide: Interim Results of the LOTUS Study
Abstract number :
1.543
Submission category :
11. Behavior/Neuropsychology/Language / 11B. Pediatrics
Year :
2025
Submission ID :
1297
Source :
www.aesnet.org
Presentation date :
12/6/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Louise Cosand, PhD – Acadia Pharmaceuticals, Inc.
Loan Robinson, BS – Acadia Pharmaceuticals, Inc.
Jenny Downs, PhD – The Kids Research Institute Australia; Curtin School of Allied Health
Rationale: Rett syndrome (RTT) is a rare neurodevelopmental disorder associated with challenges with social interaction, connection to others, and communication. Lack of effective communication has been reported by caregivers as their top concern. Trofinetide is approved for the treatment of RTT in patients aged ≥2 years in the US and patients aged ≥2 years weighing ≥9 kg in Canada. Trofinetide improved symptoms of RTT in clinical trials, evidenced by improvements on the Rett Syndrome Behaviour Questionnaire. The LOTUS study was designed to further document improvements and quality of life changes with trofinetide in patients with RTT in the real-world setting among a more diverse sample of individuals.
Methods: LOTUS is an ongoing, prospective, phase 4 study of trofinetide use in the real world. Caregivers of patients who were prescribed trofinetide under routine clinical care were eligible to participate. Behavioral improvements were assessed with the Behavioral Improvement Questionnaire (BIQ), a novel measure that solicits a “yes” or “no” response from caregivers as to whether they observed new and/or maintained behavioral improvements following treatment with trofinetide compared with the period before starting trofinetide. A “yes” answer allows caregivers to identify all areas of improvement from a checklist that included alertness, behavioral problems, breathing irregularities, communication tools, eating/swallowing, grinding teeth, mobility or balance, mood, muscle tone abnormalities, nonverbal communication, purposeful use of hands, repetitive movements, sleep, social interaction/connectedness, verbal communication, and “other” (followed by a space for free text) domains. The BIQ was assessed monthly for 6 months and every 3 months thereafter. Data are reported to 12 months since the initiation of trofinetide.
Results: In total, 227 caregivers participated in this follow-up, representing patients with ages ranging from 1 to 60 years. Most patients were female (96.9%); 7 male patients were included (3.1%). Overall, 71-90% of caregivers reported behavioral improvements with BIQ in months 1-6, 9, and 12 of trofinetide treatment. The most commonly reported behavioral improvements with BIQ were non-verbal communication (48−71%), alertness (44−70%), and social interaction/connectedness (33−58%). Other behavioral improvements reported with BIQ included mood (15−36%), use of communication tools (12−24%), and sleep (10−30%). Caregivers reported other behavioral improvements using the free-text other domain in BIQ, including improved eye contact and ambulation. Most caregivers reported 2−4 new and/or maintained behavioral improvements per month with BIQ.
Conclusions: 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.
Funding: This study was funded by Acadia Pharmaceuticals Inc.
Behavior