Trofinetide Shows Behavioral Improvements in Rett Syndrome in Phase 4 Trial

Caregivers report that treatment with trofinetide results in improvements in behavior and quality of life (QoL) for patients with Rett syndrome, according to study results presented at the 2025 American Academy of Neurology (AAN) annual meeting, held from April 5 to 9, 2025, in San Diego, California.

Trofinetide has been approved for the treatment of Rett syndrome in patients aged 2 years and older. However, information regarding real-world outcomes associated with trofinetide is limited.

Using data from the ongoing LOTUS trial, researchers conducted a 12-month follow-up to evaluate the real-world effectiveness and tolerability of trofinetide among patients with Rett syndrome.

Caregivers of patients with Rett syndrome who received trofinetide treatment completed assessments including the Behavioral Improvement Questionnaire (BIQ), the Quality-of-Life Inventory Disability (QI-Disability) questionnaire, and the Gastrointestinal (GI) Health questionnaire.

A total of 192 patients (median age at diagnosis, 3 years; girls and women, 95.8%) with Rett syndrome were included in the study. Median dose of trofinetide was 45.0% of the target weight-banded label dose at week 1 and at least 80% at week 9 onwards.

Data collected from the BIQ indicated behavioral improvements including nonverbal communication (49%-62%), alertness (43%-62%), and social interaction/connectedness (32%-52%).

Using the QI-Disability questionnaire, overall improvements in patients’ QoL with trofinetide were observed.

On the GI Health questionnaire, caregivers noted that patients were most likely to void normal stools during the follow-up period, with diarrhea contained within the diaper.

Overall, response to trofinetide was similar among pediatric and adult patients.

“Caregivers of patients with [Rett syndrome] in LOTUS reported behavioral improvements of RTT symptoms and improvement in patients’ QOL,” the researchers concluded.

Multiple authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.