FDA Grants Acadia Priority Review for Rett Syndrome Therapy

The U.S. Food and Drug Administration (FDA) has granted Priority Review to Acadia Pharmaceuticals’ New Drug Application for trofinetide, the company’s experimental therapy for the treatment of Rett syndrome.

Photo: Steve Davis, CEO of Acadia

The FDA has set a date of March 12, 2023 as a target date to act on the application.

Rett syndrome is a complex, multisystem neurodevelopmental disorder that includes a period of normal development followed by significant developmental regression with loss of language and hand function skills, impaired gait, and development of hand stereotypes. It occurs worldwide in approximately one of every 10,000 to 15,000 female births.

Trofinetide is an investigational drug. It 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. Trofinetide is thought to stimulate synaptic maturation and overcome the synaptic and neuronal immaturities that are characteristic of Rett syndrome pathophysiology. In the central nervous system, IGF-1 is produced by both of the major types of brain cells – neurons and glia. IGF-1 in the brain is critical for both normal development and for response to injury and disease. Trofinetide has been shown to inhibit the production of inflammatory cytokines, inhibit the overactivation of microglia and astrocytes, and increase the amount of available IGF-1 that can bind to IGF-1 receptors.

The NDA is supported by results from the pivotal phase 3 Lavender study evaluating the efficacy and safety of trofinetide versus placebo in 187 girls and young women aged 5-20 years with Rett syndrome. The study demonstrated a statistically significant improvement over placebo on the co-primary endpoints, the Rett Syndrome Behavior Questionnaire (RSBQ) total score change from baseline to 12 weeks and the Clinical Global Impression-Improvement (CGI-I) scale score. The RSBQ is a caregiver assessment of the core symptoms of Rett syndrome, and the CGI-I is a global physician assessment of worsening or improving of Rett syndrome. In addition, the study also met its key secondary endpoint, the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist–Social Composite Score change from baseline to week 12 (p=0.0064; effect size=0.43), a caregiver assessment of ability to communicate.

In 2018, Acadia entered into an exclusive license agreement with Neuren Pharmaceuticals for the development and commercialization of trofinetide for the treatment of Rett syndrome and other indications in North America. In addition to receiving priority review by the FDA, trofinetide has been granted Fast Track status and Orphan Drug designation for the treatment of Rett syndrome in the U.S. and has been granted Rare Pediatric Disease designation by the FDA. Upon FDA approval of a product with RPD designation, the sponsor can receive a Priority Review Voucher, which can be used to obtain priority review for a subsequent application.

“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,” said Steve Davis, Acadia’s CEO.

Author: Rare Daily Staff