2.2 Dementia-Related Psychosis

Trofinetide – Rett syndrome


Trofinetide is a novel synthetic analog of the amino‐terminal tripeptide of IGF-1 designed to treat the core symptoms of Rett syndrome by reducing neuroinflammation and supporting synaptic function. Acadia has an exclusive license to develop and commercialize trofinetide in North America from Neuren Pharmaceuticals.

About Rett syndrome

Rett syndrome is a debilitating neurological disorder that occurs primarily in females following apparently normal development for the first six months of life. Rett syndrome has been most often misdiagnosed as autism, cerebral palsy, or non-specific developmental delay. Rett syndrome is caused by mutations on the X chromosome on a gene called MECP2. There are more than 200 different mutations found on the MECP2 gene that interfere with its ability to generate a normal gene product. Rett syndrome occurs worldwide in approximately one of every 10,000 to 15,000 female births (6,000 to 9,000 patients in the U.S.) causing problems in brain function that are responsible for cognitive, sensory, emotional, motor, and autonomic function. Typically, between 6 to 18 months of age, patients experience a period of rapid decline with loss of purposeful hand use and spoken communication and inability to independently conduct activities of daily living. Symptoms also include seizures, disorganized breathing patterns, an abnormal side-to-side curvature of the spine (scoliosis), and sleep disturbances. Currently there are no approved medicines for the treatment of Rett syndrome.


Positive top-line results from the Phase 3 LavenderTM study evaluating trofinetide, an investigational drug for the treatment of Rett syndrome, were announced in December of 2021.

The Lavender study evaluated the efficacy and safety of trofinetide in 187 girls and young women aged 5-20 years with Rett syndrome. The 12-week placebo-controlled study demonstrated a statistically significant improvement over placebo for both co-primary endpoints. On the Rett Syndrome Behaviour Questionnaire (RSBQ), change from baseline to week 12 was -5.1 vs. -1.7 (p=0.0175; effect size = 0.37). 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 physician assessment of worsening or improving of Rett syndrome.

Trofinetide also met the key secondary endpoint, demonstrating a statistically significant separation over placebo in the Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist–Social composite score (CSBS-DP-IT–Social) change from baseline to week 12 (-0.1 vs. -1.1; p=0.0064; effect size = 0.43).

All patients completing the Lavender study were eligible for the LILAC study, a 40-week extension study in which all participants will receive trofinetide and followed to evaluate long-term tolerability, safety, and effectiveness of the drug.

The safety and efficacy of trofinetide have not been reviewed or approved by the U.S. Food and Drug Administration (FDA). As a next step, Acadia is planning for a meeting with the FDA in the first quarter of 2022 and plans to submit a new drug application (NDA) around mid-year 2022.

Trofinetide has been granted Fast Track Status and Orphan Drug Designation for Rett syndrome. Trofinetide has also been granted Rare Pediatric Disease (RPD) designation by the FDA. An NDA with Orphan Drug Designation is eligible for priority review. A RPD NDA can be awarded a Priority Review Voucher if approved, subject to final determination by the FDA.

Rett Community Updates