Rett Syndrome Treatment Receives Priority Review from FDA

After filing a new drug application (NDA) regarding trofinetide for the treatment of Rett syndrome, Acadia Pharmaceuticals announced that the FDA granted a priority review for the investigational drug and set March 12, 2023 as the Prescription Drug User Fee Act (PDUFA) date.

Rett syndrome is a multisystem disease that has a significant impact on the central nervous system leading to the loss of communication ability, intentional hand use, gait abnormalities, and stereotypic hand movements including hand wringing, squeezing, clapping, tapping, mouthing and washing or rubbing automatisms.

Additional symptoms that can manifest in individuals with the rare disease are gastrointestinal complications, skeletal abnormalities, neuroendocrine abnormalities, disruptive and anxiety-like behaviors, as well as mood dysregulation and sleep disruption.

The novel therapy is a synthetic analog of animno-terminal peptide of IGF-1. Because Rett syndrome is caused by mutations of the X chromosome on the MECP2 gene, the aim of trofinetide is to stimulate synaptic maturation and surpass the synaptic and neuronal immaturities that result from these mutations, addressing the core symptoms.

“Rett is a complex disease that can present with a diverse array of symptoms. In clinical trials, trofinetide demonstrated a significant improvement in a range of Rett syndrome symptoms. We look forward to the FDA’s review of this submission and the prospect of having access to the first approved treatment for Rett syndrome," Jeffrey L. Neul, MD, PhD, Vanderbilt Kennedy Center, Division of Neurology, Pharmacology, and Special Education, Vanderbilt University Medical Center and Phase 3 Lavender study investigator said in a statement.

The FDA decision was supported by phase 3 data provided by the Lavender study which evaluated the safety and efficacy of trofinetide compared with placebo. The study consisted of 187 girls and women with Rett syndrome between the ages of 5-20.

A statistically significant improvement on the Rett Syndrome Behavior Questionnaire (RSBQ) total score and the Clinical Global Impression-Improvement (CGI-I) scale score was observed by investigators after 12 weeks, therefore fulfilling the co-primary endpoints.

The FDA also provided trofinetide with Rare Pediatric Disease (RPD) designation and Fast Track Status and Orphan Drug Designation for the treatment of Rett syndrome in the US. When a drug with RPD designation is approved, a Priority Review Voucher is given to the sponsor to obtain priority review for a subsequent application.

“We’re pleased that the FDA has accepted our NDA filing and we will be working closely with them to facilitate completion of the review in a timely manner,” Steve Davis, CEO of Acadia said in a statement.

“If approved, trofinetide will be the first drug available for the treatment of Rett syndrome, a rare and devastating condition for patients and their families," he continued. "This milestone reinforces Acadia’s ongoing commitment to advancing research into high unmet needs in disorders affecting the central nervous system.”