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.

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 causing problems in brain function that are responsible for cognitive, sensory, emotional, motor and autonomic function. Typically, between six to eighteen 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.


In the second half of 2019, we plan to initiate a 12-week Phase 3, double-blind, randomized, placebo-controlled study to evaluate efficacy and safety of trofinetide and placebo in approximately 180 females ages 5 to 20 years with Rett syndrome. Half of the study participants will receive trofinetide and half will receive placebo. The study will use the Rett Syndrome Behaviour Questionnaire (RSBQ), a caregiver assessment and the Clinical Global Impression Scale-Improvement (CGI-I), a clinician assessment of the improvement of Rett syndrome as co-primary efficacy endpoints.

The Phase 3 study will be followed by an open label extension study in which all participants, including those on placebo in the Phase 3 study, will be eligible to receive trofinetide. In the open label extension study, all participants will be followed to evaluate long term tolerability and safety of trofinetide.

Trofinetide has been granted Fast Track Status and Orphan Drug Designation for Rett syndrome in the U.S. and Orphan Drug Designation for Rett syndrome in Europe.

ACADIA has an exclusive license to develop and commercialize trofinetide in North America from Neuren Pharmaceuticals.