Haya Mayman,¹ Jenny Downs,^2,3 Louise Cosand¹

¹ Acadia Pharmaceuticals Inc., San Diego, CA, USA

² The Kids Research Institute Australia, The Centre for Child Health Research, University of Western Australia, Perth, WA, Australia

³ Curtin School of Allied Health, Faculty of Health Sciences, Curtin University, Perth, WA, Australia

Objective: To characterize the real-world benefits and tolerability of trofinetide in the treatment

of Rett syndrome (RTT) using the 12-month follow-up of the ongoing LOTUS study.

Background: Trofinetide is approved for the treatment of RTT in patients aged ≥2 years in the

United States and patients aged ≥2 years weighing at least 9 kg in Canada. Results from

quantitative measures from trofinetide clinical trials have generated interest among clinicians

and caregivers in practical, real-world outcomes associated with trofinetide treatment.

Design/Methods: LOTUS is an ongoing, prospective study of patients with RTT prescribed

trofinetide in real-world clinical practice. Caregivers of patients who are prescribed trofinetide

under routine clinical care are eligible to participate. Assessments include the Behavioral

Improvement Questionnaire (BIQ), the Quality-of-Life Inventory-Disability (QI-Disability)

Questionnaire, and the Gastrointestinal Health Questionnaire. Due to ongoing enrollment, data

are reported to 9 months since the initiation of trofinetide.

Results: In total, 192 patients were included in this follow-up. The median dose reported at

week 1 was 45.0% of the target weight-banded label dose; by week 9 onwards, the median

dose was at least 80.0% of the target weight-banded label dose. Behavioral improvements

reported with the BIQ were nonverbal communication (49–62%), alertness (43–62%), and social

interaction/connectedness (32–52%). The QI-Disability Questionnaire median total scores

indicated overall improvement in patient quality of life (QoL) with trofinetide. Caregivers reported

that patients were most likely to void normal stools over the follow-up; most reports of diarrhea

were contained inside the patient’s diaper. Response patterns to trofinetide were similar among

pediatric and adult patients, suggesting that trofinetide responses do not clearly differ across

age groups.

Conclusions: Caregivers of patients with RTT in LOTUS reported behavioral improvements of

RTT symptoms and improvement in patients’ QoL.