On Mar. 13, 2023, the U.S. Food and Drug Administration (FDA) announced that it had approved Acadia Pharmaceuticals’ Daybue (trofinetide) oral solution as the first treatment for Rett syndrome, a rare, genetic neurological disorder. Daybue is approved for the treatment of Rett syndrome in adults and children 2 years of age and older.

Rett syndrome is a rare, genetic neurological and developmental disorder that affects the way the brain develops. Patients with Rett syndrome experience a progressive loss of motor skills and language. Most babies with Rett syndrome seem to develop as expected for the first six months of life. These babies then lose skills they previously had attained at approximately six to 18 months of age — such as the ability to crawl, walk, communicate, or use their hands. The hallmark of Rett syndrome is near constant repetitive hand movements, such as rubbing or clapping. Rett syndrome leads to severe impairments affecting nearly every aspect of life, including the ability to speak, walk, eat, and breathe. The syndrome primarily affects females (1 in 10,000) and even more rarely affects males.

The efficacy and safety of Daybue was evaluated in a randomized, double-blind, placebo-controlled, 12-week study of patients with Rett syndrome five to 20 years of age. Patients were randomized to receive Daybue (N=93) or matching placebo (N=94) for 12 weeks. The dose of Daybue was based on patient weight to achieve similar exposure in all patients.

The co-primary efficacy measures were change from baseline in the Rett Syndrome Behavior Questionnaire (RSBQ) total score and the Clinical Global Impression-Improvement (CGI-I) score at week 12. The RSBQ is a 45-item rating scale completed by the caregiver that assesses a range of signs and symptoms of Rett syndrome. Lower scores represented lesser severity in signs and symptoms of Rett syndrome. The CGI-I is a 7-point scale rated by clinicians to assess how much a patient’s illness has improved or worsened. A decrease in CGI-I score indicates improvement.

Patients treated with Daybue demonstrated a statistically significant difference compared to placebo on the co-primary efficacy endpoints, as measured by the change from baseline in the RSBQ total score and the CGI-I score at week 12. Daybue received priority review, orphan drug and fast track drug designations.