Acadia Pharmaceuticals Inc. has announced the submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for trofinetide, a synthetic analog of the N-terminal tripeptide of insulin-like growth factor 1 (IGF-1), for the treatment of Rett syndrome in adults and pediatric patients aged two years and older. This marks a significant step towards potentially providing the first approved therapy for this rare neurodevelopmental disorder in the European Union (EU). Trofinetide is already approved in the United States and Canada for the same indication.
Phase 3 LAVENDER Study Supports MAA
The MAA is supported by data from the pivotal Phase 3 LAVENDER study, a randomized, double-blind, placebo-controlled trial involving 187 girls and young women aged 5 to 20 years with Rett syndrome. The study evaluated the efficacy and safety of trofinetide compared to placebo over a 12-week treatment period.
The co-primary endpoints of the LAVENDER study were the change from baseline in the Rett Syndrome Behaviour Questionnaire (RSBQ) total score, a caregiver assessment, and the Clinical Global Impression–Improvement (CGI-I) scale score, a clinician's perspective. Both endpoints demonstrated statistically significant improvements in the trofinetide group compared to placebo.
Additionally, the key secondary endpoint, measuring the change from baseline to week 12 in the Communication and Symbolic Behavior Scales Development Profile Infant-Toddler Checklist–Social composite score (CSBS-DP-IT–Social), also showed statistically significant improvement with trofinetide compared to placebo.
Addressing Unmet Needs in Rett Syndrome
Rett syndrome is a rare, complex neurodevelopmental disorder primarily affecting females, occurring in approximately 1 in every 10,000 to 15,000 female births worldwide. The disorder typically manifests in four stages, characterized by a period of normal development followed by a slowing or stagnation of skills between 6 and 18 months of age. This is often followed by a regression phase involving loss of communication skills and purposeful hand use. As individuals with Rett syndrome age, they may experience motor deterioration and require round-the-clock care.
"This application underscores our continued dedication to the Rett community, and our commitment to making a meaningful impact for people living with Rett syndrome and their caregivers in the EU, who currently have no approved treatment options specifically for this condition," said Catherine Owen Adams, Acadia’s Chief Executive Officer. "We look forward to working with the EMA to address this unmet need in the hopes of potentially bringing this therapy to families who are impacted by Rett syndrome."
Trofinetide's Mechanism of Action
Trofinetide is a synthetic analog of the N-terminal tripeptide of insulin-like growth factor 1 (IGF-1). While the precise mechanism by which trofinetide exerts its therapeutic effects in Rett syndrome is not fully understood, animal studies have shown that it can increase branching of dendrites and synaptic plasticity signals, potentially improving neuronal communication.
If approved by the EMA, trofinetide would represent a significant advancement in the treatment of Rett syndrome in the European Union, offering a potential therapeutic option to address the unmet medical needs of patients and their families.
