Acadia Submits NDA for Trofinetide


If approved, this would be the first therapy to treat patients with Rett syndrome, a rare genetic neurological disorder mostly in girls.

Acadia Pharmaceuticals has submitted a new drug application (NDA) to the FDA for trofinetide for the treatment of Rett syndrome in adults and pediatric patients two years of age and older. Rett syndrome is rare genetic neurological disorder mostly seen in girls, and is caused by mutations on the X chromosome on a gene called MECP2. It causes progressive loss of motor skills and the ability to communicate.

If approved, this would be the first therapy to treat patients with Rett syndrome, a rare genetic neurological disorder in girls. Treatment is currently focused on managing symptoms.

The NDA submission 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) change from baseline to 12 weeks and the Clinical Global Impression-Improvement (CGI-I) scale score at 12 weeks. In the RSBQ, a caregiver assessment of the core symptoms of Rett syndrome, the score for trofinetide was -5.1 compared with -1.7 for placebo. In the CGI-I, a global physician assessment of worsening or improving of Rett syndrome, the score for trofinetide was 3.5 compared with 3.8 for placebo.

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, a caregiver scale of the ability to communicate.

Jeffrey L. Neul, M.D., Ph.D.

Jeffrey L. Neul, M.D., Ph.D.

“These are encouraging results for patients and families affected by Rett syndrome. Patients reported improvements in core symptoms, like being able to respond to a choice when asked by their parents, or experiencing more freedom from the repetitive hand movements that create obstacles in other areas of their lives,” Jeffrey L. Neul, M.D., Ph.D., Annette Schaffer Eskind Chair and director, Vanderbilt Kennedy Center, said in a press release when top-line results were released. He is also professor of Pediatrics, Division of Neurology, Pharmacology, and Special Education, Vanderbilt University Medical Center and Lavender study investigator.

Treatment discontinuation rates related to adverse events were 17.2% in the trofinetide group compared with 2.1% in the placebo group. The most common adverse events were diarrhea and vomiting, which were considered mild-to-moderate. Serious adverse events were experienced by 3.2% of study participants in both the trofinetide and placebo groups.

Patients who completed the Lavender study had the opportunity to continue to receive trofinetide in the open-label Lilac and Lilac-2 extension studies. More than 95% of participants who completed the Lavender study elected enroll in open-label extension study. The results from this study will be submitted for presentation at upcoming medical meetings.

Trofinetide is a novel synthetic analog of the amino‐terminal tripeptide of insulin-like growth factor 1 (IGF-1) designed to treat the core symptoms of Rett syndrome by reducing neuroinflammation and supporting synaptic function

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.

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