News|Articles|September 15, 2025

Phase IV Trial Shows Daybue Demonstrates Real-World Behavioral Improvements in Rett Syndrome

Interim results from the ongoing Phase IV LOTUS trial showed that Daybue delivered sustained behavioral improvements and manageable gastrointestinal outcomes in Rett syndrome patients over one year.

Topline Findings

Real-world effectiveness: Daybue demonstrated meaningful behavioral improvements in 71% to 90% of Rett syndrome patients, particularly in nonverbal communication, alertness, and social interaction.

Quality-of-life gains: Patients with baseline and 12-month assessments showed a median 4.6-point improvement on the Quality-of-Life Inventory-Disability scale, reflecting sustained functional benefits.

Manageable safety profile: Gastrointestinal adverse events, primarily diarrhea, were reported in 23% to 50% of patients early in treatment and 26% to 38% later, with most cases mild to moderate and effectively managed through supportive measures.

Results from an interim analysis of the ongoing Phase IV LOTUS trial showed that Acadia Pharmaceuticals’ Daybue (trofinetide) demonstrated meaningful behavioral gains and quality-of-life improvements in Rett syndrome. According to the company, these findings reinforce confidence in Daybue’s role as the first FDA-approved treatment for Rett syndrome and highlight its potential to meet long-standing unmet needs for patients and caregivers.¹

How is Daybue Performing in Real-World Rett Syndrome Patients?

“These findings from LOTUS help deepen our understanding of the potential outcomes associated with long-term treatment of Daybue in the real-world setting,” said Ponni Subbiah, MD, MPH, SVP, global head, medical affairs, chief medical officer, Acadia Pharmaceuticals, in a press release.

LOTUS Trial Design & Methods

The interim analysis of the observational, real-world, prospective LOTUS trial evaluated the real-world effectiveness and tolerability of Daybue in 227 patients with Rett syndrome in the United States.
In consultation with Rett experts, caregivers completed online questionnaires developed specifically for this study—including the Behavioral Improvement Questionnaire and the Gastrointestinal Health Questionnaire. Additional validated tools, such as the Quality-of-Life Inventory-Disability Questionnaire, were used.
Patients were followed for at least one year, with the option to extend participation for an additional year.
The primary endpoint of the trial was to describe the real-world effects of Daybue through the use of an 18-month follow up analysis.^1,2

Key Interim Results

Results showed that 71% to 90% of caregivers reported at least one new or maintained behavioral improvement in patients receiving Daybue.
The most commonly reported improvements were in nonverbal communication, observed in 48% to 71% of patients; alertness, seen in 44% to 70%; and social interaction and connectedness reported in 33% to 58% of patients.
Quality-of-life assessments showed a median improvement of 4.6 points on the QI-Disability scale among patients with both baseline and 12-month data.
Median dosing reached at least 80% of the target FDA-approved dose by week 10, up from 36% at week one.
The most commonly observed adverse event related to gastrointestinal tolerability was diarrhea, reported in 23% to 50% of patients during weeks one to 12 and 26% to 38% during months four to 12.
Most cases were mild to moderate, contained within the patient’s diaper, and managed effectively with supportive measures, such as increased fluid intake, fiber supplementation, or use of antidiarrheal medications.^1,2

Rett Syndrome Overview

According to Acadia, Rett syndrome affects approximately one in 10,000 to 15,000 female births globally, with an estimated 6,000 to 9,000 patients in the United States.
It usually begins with a period of seemingly normal development until the patient reaches six to 18 months of age, followed by regression in which acquired communication skills and purposeful hand movements are lost.¹
According to the National Organization for Rare Diseases, it is the second most common cause of severe intellectual disability after Down syndrome.
Roughly 90% to 95% of Rett syndrome cases are linked to detectable mutations in the MECP2 gene, with over 200 distinct mutations documented. In approximately 99% of instances, these mutations arise spontaneously and are neither inherited from nor carried by the child’s parents.³

“The data are supportive of what we’ve seen in Daybue clinical trials and offer new scientific insights to clinicians that improvements in Rett syndrome signs and symptoms are possible among a broadly inclusive sample of Rett patients,” continued Subbiah, in the press release. “It’s particularly gratifying to document improvements in adult patients, knowing that they may have waited decades without knowing if a treatment would become available within their lifetime.”

References

Real World Data from LOTUS Study Evaluating Long-term Efficacy and Tolerability Outcomes of DAYBUE® (trofinetide) in Patients with Rett Syndrome Published in Developmental Medicine and Child Neurology. BusinessWire. September 12, 2025. Accessed September 15, 2025. https://www.businesswire.com/news/home/20250911498207/en/Real-World-Data-from-LOTUS-Study-Evaluating-Long-term-Efficacy-and-Tolerability-Outcomes-of-DAYBUE-trofinetide-in-Patients-with-Rett-Syndrome-Published-in-Developmental-Medicine-and-Child-Neurology
Real-world benefits and tolerability of trofinetide for the treatment of Rett syndrome: The LOTUS study. Wiley. Accessed September 15, 2025. https://onlinelibrary.wiley.com/doi/10.1111/dmcn.16482
Rett Syndrome. NORD. Accessed September 15, 2025. https://rarediseases.org/rare-diseases/rett-syndrome/#causes

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