Ryan Bucco, PharmD, Vice President of Medical Affairs in Rare Disease at Acadia, discusses the LOTUS study in patients with Rett syndrome treated with Daybue (trofinetide).
Rett syndrome is a neurodevelopmental condition that primarily affects girls. People with the disease appear to have normal psychomotor development during the first 6 to 18 months of life, followed by a developmental “plateau,” and then rapid regression in language and motor skills. Additional signs and symptoms may include repetitive, stereotypic hand movements, fits of screaming and inconsolable crying, autistic features, panic-like attacks, teeth grinding, episodic apnea and/or hyperpnea, gait ataxia and apraxia, tremors, seizures, and slowed head growth. Classic Rett syndrome is most commonly caused by genetic changes in the MECP2 gene.
At the 2026 IRSF Rett Syndrome Scientific Meeting, real-world benefits and tolerability of trofinetide for the treatment of patients with atypical rett syndrome in the LOTUS study were presented. LOTUS is an ongoing, caregiver reported, real world, observational phase 4 study designed to better understand how trofinetide is being used and tolerated in routine clinical practice and to capture caregiver reported experiences over time.
Trofinetide is a synthetic analog of the N-terminal tripeptide of insulin-like growth factor-1, approved for treatment of Rett syndrome in 2023. Daybue Stix is an oral, dye- and preservative-free powder formulation of the treatment approved in December 2025 and now available in the US for patients 2 years of age and older. The objective with this new formula was to address concerns related to taste, dosing volume, portability, dietary restrictions, and food sensitivities.
The goal of this study was to describe the real-world effects of trofinetide in individuals with Rett syndrome using the 18-month follow-up analysis of the LOTUS study.
A total of 227 caregivers participated in this analysis. The median trofinetide dose at week 1 was 36% of the target dose and increased to over 80% by week 10 onwards. 55.2% of patients took the full trofinetide recommended daily dose. Caregivers (71%-90%) reported behavioral improvements across months 1 to 12 with the Behavioral Improvement Questionnaire (BIQ), including non-verbal communication (48%-71%), alertness (44%-70%), and social interaction and connectedness (33%-58%). The median Quality of Life Inventory-Disability (QI-Disability) total score change from baseline ranged from 4.7 to 4.6 in months 1 to 12. The incidence of diarrhea varied from weeks 1 to 12 (23%-50%) and months 4 to 12 (26%-38%); most reports of diarrhea were contained inside the patient’s diaper. Safety reports were consistent with previous trofinetide clinical trials.
Dr. Bucco also highlights the differences in findings between subgroups including patients with atypical Rett syndrome and male patients with Rett syndrome.
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To learn more about Rett syndfome and other rare genetic conditions, visit https://checkrare.com/diseases/congenital-and-genetic-conditions/