Trofinetide improves behavioral, physical outcomes in Rett syndrome at 9 months

Key takeaways:

• Caregivers reported improvements in patients’ nonverbal communication, alertness and social interactions.
• Outcomes also improved with respect to quality-of-life metrics and gastrointestinal issues.

SAN DIEGO — Among individuals with Rett syndrome, treatment with trofinetide was linked to improvements in caregiver-reported outcomes by 9 months, according to a speaker at the American Academy of Neurology Annual Meeting.

“Rett syndrome is a rare neurodevelopmental disorder that involves a patient who presents typically at birth and goes through a regression in early childhood,” Louise Cosand, PhD, medical director in rare disease at Acadia Pharmaceuticals, which sponsored the study, said during her presentation. “The regression predominantly affects hand use, speech and ambulation.”

As clinicians and patients’ families have a vested interest in real-world outcomes for novel therapeutics that address Rett syndrome, Cosand and colleagues sought to examine safety and efficacy of trofinetide (Daybue, Acadia) in the ongoing, phase 4 LOTUS trial. Cosand presented interim results of the trial with data up to 9 months during a late-breaking session at AAN.

LOTUS is an observational, prospective study in which caregivers of 192 individuals (median age at diagnosis, 3 years; 95.8% girls and women) prescribed trofinetide as routine clinical care for all types of Rett syndrome are tasked with providing patient assessments based on behavior, quality-of-life and gastrointestinal health concerns.

According to the results, between 69% and 81% of caregivers noted behavioral improvements from months 1 to 9, with a range of 59% to 77% of improvements recorded in adult patients and 76% to 85% in pediatric patients.

The researchers also found that scores on quality-of-life disability questionnaires indicated improvements from baseline, with similar trends apparent for domains such as social interaction, physical health, well-being, positive and negative emotions, as well as outdoor leisure activities.

Data further showed that trofinetide improved containment and management strategies related to gastrointestinal issues in the pediatric population, with varied levels of incidence between weeks 1 through 12 and months 4 through 9 and the highest incidence logged at week 6 by 55% of caregivers.

Cosand and colleagues noted that these interim results were limited by several factors, including the number of caregiver reports, the number of patients to reach later timepoints within the study, as well as the online format of the study. They added that further analyses will be conducted as more patients are enrolled.

“This is the fourth interim analysis; each time we have seen the top three results to be nonverbal communication improvements, alertness and social interaction and connectedness,” Cosand said.

Editor's Note: This story was corrected on April 14, 2025 to reflect caregivers' reporting that patients' nonverbal communication improved with trofinetide.