Long-Term Data of Trofinetide in Patients With Rett Syndrome

Ponni Subbiah, MD, Senior Vice President of Acadia, Global Head of Medical Affairs and Chief Medical Officer, discusses long-term data from clinical trial extension of trofinetide in patients with Rett syndrome.

Rett syndrome is a neurodevelopmental condition primarily affecting girls. Classic Rett syndrome is most commonly caused by genetic changes in the MECP2 gene. 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
- Slowed head growth

Trofinetide is a synthetic analog of the N-terminal tripeptide of insulin-like growth factor 1. It was approved by the U.S. Food and Drug Administration for the treatment of Rett syndrome in patients 2 years and older in 2023. LILAC-1 was a 40-week, open-label extension of the phase 3 LAVENDER trial evaluating the long-term safety and efficacy of trofinetide in patients ages 5 to 21 years with Rett syndrome. LILAC-2 was a 32-month open-label extension evaluating the long-term safety and efficacy of trofinetide in female patients, ages 5 to 22 years who completed LILAC-1.

Patients who completed these studies experienced an improvement in symptoms as measured by the Rett Syndrome Behaviour Questionnaire (RSBQ). Patients from the LAVENDER trial were eligible for the 40-week LILAC-1 study (n=154), and then, the 32- week LILAC-2 (n=77) study. 27 caregivers participated in an optional exit interview to observe their experiences with Rett syndrome and the trofinetide treatment during the studies. The most frequent improvements that caregivers reported were engagement with others (46.2%), hand use (42.3%), eye gaze (30.8%), new sounds (23.1%), and new words (19.2%).

Additionally, no new safety concerns were observed with profiles consistent with that observed in the LAVENDER trial. The most common side effects were diarrhea and vomiting.