Jeffrey Neul, MD, PhD, Professor of Pediatrics at Vanderbilt University Medical Center, discusses recent top-line results from a phase 3 trial testing trofinetide to treat children with Rett syndrome.

Trofinetide is an analog of insulin-like growth factor 1 (IGF-1) and it is speculated that the orphan drug can restore homeostasis of neuronal signaling in diseases such as Rett syndrome.

​​Rett syndrome is a rare progressive neurodevelopmental condition that primarily affects girls. These girls 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. Common symptoms include hand-wringing; fits of screaming and inconsolable crying; autistic features; panic-like attacks; bruxism; episodic apnea and/or hyperpnea; gait ataxia and apraxia; tremors; seizures; and slowed head growth. Rett syndrome is most commonly caused by a sporadic mutation in the MECP2 gene on the X chromosome. The majority of cases are not inherited from a parent. 

Recently, positive top-line results from the Lavender study were announced. As Dr. Neul explains, the Lavender study (NCT04181723)  is a phase 3 study evaluating the safety and efficacy of trofinetide in 187 Rett syndrome patients aged 5 to 20 years. Trofinetide met co-primary efficacy endpoints demonstrating statistically significant improvement over placebo in the Rett Syndrome Behaviour Questionnaire (RSBQ) and the Clinical Global Impression of Improvement (CGI-I). On the Rett Syndrome Behaviour Questionnaire (RSBQ), change from baseline to week 12 was -5.1 in the trofinetide arm vs. -1.7 in the placebo arm (P=.0175). The Clinical Global Impression–Improvement (CGI-I) score at week 12 was 3.5 vs. 3.8 (p=0.0030; effect size=0.47). The RSBQ is a caregiver assessment of the core symptoms of Rett syndrome and the CGI-I is a global physician assessment of worsening or improving Rett syndrome.

Additionally, trofinetide demonstrated a statistically significant separation over placebo on the key secondary endpoint, the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist–Social composite score (CSBS-DP-IT–Social) change from baseline to week 12 was -0.1 vs. -1.1 (P=.0064).

According to Dr. Neul, next steps following these results include two open-label extension studies as well as for the sponsor to organize a New Drug Admission (NDA) to the U.S. Food and Drug Administration. This NDA package is expected to be submitted some time this year. 

For more information about Rett syndrome and other rare neurological disorders, visit