Trofinetide Treatment of Rett Syndrome Provides Clinician- and Caregiver-Rated Improvement

A phase 3 study that evaluated the efficacy and safety of the investigational drug achieved positive topline results. The 12-week, placebo-controlled study demonstrated a statistically significant improvement in for both coprimary endpoints.

In the LAVENDER study (NCT04181723), individuals with Rett syndrome treated with trofinetide (Acadia Pharmaceuticals, San Diego, CA) had caregiver-reported improvement in behavior. Change from baseline to week 12 on the Rett Syndrome Behaviour Questionnaire (RSBQ) was -5.1 vs. -1.7 (P=.0175; effect size=0.37). Clinician rating of improvement on the Clinical Global Impression-Improvement (CGI-I) score at week 12 was 3.5 vs. 3.8 (P=.0030; effect size=0.47).  

“These are encouraging results for patients and families affected by Rett syndrome,” said Jeffrey L. Neul, MD, PhD, professor of pediatrics, division of neurology, pharmacology, and special education, Vanderbilt University Medical Center. “(Caregivers) reported improvements in core symptoms, like being able to respond to a choice when asked by their parents or experiencing more freedom from the repetitive hand movements that create obstacles in other areas of their lives. The positive LAVENDER study results support a potential treatment for Rett syndrome and represent an important step forward in addressing this rare and serious neurologic disease.” 

Study treatment discontinuation rates related to treatment-emergent adverse events were 17.2% in the trofinetide group compared to 2.1% in the placebo group. The most common adverse events were diarrhea (80.6% with trofinetide vs. 19.1% with placebo), of which 97.3% instances in the trofinetide arm were characterized as mild-to-moderate; and vomiting (26.9% with trofinetide vs. 9.6% with placebo), of which 96% in the trofinetide arm were characterized as mild-to moderate. Serious adverse events were observed in 3.2% of study participants in both the trofinetide and placebo groups.

Trofinetide is a novel synthetic analog of the amino-terminal tripeptide of IGF-1 designed to treat the core symptoms of Rett syndrome by potentially reducing neuroinflammation and supporting synaptic function.