FDA Greenlights Daybue for Treatment of Rett Syndrome

Credit: Acadia Pharmaceuticals.
The approval was supported by data from the randomized, double-blind, placebo-controlled phase 3 LAVENDER study.

The Food and Drug Administration (FDA) has approved Daybue (trofinetide) for the treatment of Rett syndrome in adults and pediatric patients 2 years of age and older.

Trofinetide is a novel synthetic analogue of glycine-proline-glutamate, the amino-terminal tripeptide of insulin-like growth factor-1. Though the mechanism by which trofinetide exerts its therapeutic effects in patients with Rett syndrome is unknown, it is believed to increase branching of dendrites and synaptic plasticity signals based on animal studies.

The approval was supported by data from the randomized, double-blind, placebo-controlled phase 3 LAVENDER study (ClinicalTrials.gov Identifier: NCT04181723), which evaluated the efficacy and safety of trofinetide in female patients 5 to 20 years of age with Rett syndrome. Patients were randomly assigned to receive trofinetide (n=93) or placebo (n=94) orally or via gastrostomy tube twice daily for 12 weeks. 

The coprimary endpoints were the change from baseline to week 12 in the Rett Syndrome Behaviour Questionnaire (RSBQ) total score (a caregiver assessment) and the Clinical Global Impression-Improvement (CGI-I) score (a physician assessment). Lower scores reflect lesser severity in signs and symptoms of Rett syndrome.

Treatment with trofinetide was associated with a statistically significant improvement on the RSBQ compared with placebo (-4.9 vs -1.7; treatment difference, -3.2 [95% CI, -5.7, -0.6]; P =.018). A statistically significant improvement over placebo was also observed on the CGI-I (3.5 vs 3.8; treatment difference, -0.3 [95% CI, -0.5, -0.1]; P =.003). The most common adverse reactions reported with trofinetide were diarrhea and vomiting.

“Rett syndrome is a profoundly debilitating and complex, rare, neurodevelopmental disorder that presents differently across patients and can lead to an array of unpredictable symptoms throughout the course of a patient’s life,” said Jeffrey L. Neul, MD, PhD, Annette Schaffer Eskind Chair and Director, Vanderbilt Kennedy Center, Professor of Pediatrics, Division of Neurology, Pharmacology, and Special Education, Vanderbilt University Medical Center and Phase 3 LAVENDER study investigator. “Now, for the first time after decades of clinical research, health care providers finally have a treatment option to address a range of core behavioral, communication and physical symptoms for their patients living with Rett syndrome.”

Daybue is supplied as a strawberry-flavored oral solution containing 200mg of trofinetide per mL. The dosage is determined by patient weight and can be administered orally or via gastrostomy tube. The product is expected to be available by the end of April 2023.


  1. Acadia Pharmaceuticals announces US FDA approval of Daybue™ (trofinetide) for the treatment of Rett syndrome in adult and pediatric patients two years of age and older. News release. Acadia Pharmaceuticals. March 10, 2023. https://www.businesswire.com/news/home/20230303005382/en/Acadia-Pharmaceuticals-Announces-U.S.-FDA-Approval-of-DAYBUE%E2%84%A2-trofinetide-for-the-Treatment-of-Rett-Syndrome-in-Adult-and-Pediatric-Patients-Two-Years-of-Age-and-Older.
  2. Daybue. Package insert. Acadia Pharmaceuticals; 2023. Accessed March 13, 2023. https://acadia.com/wp-content/uploads/2023/03/daybue-prescribing-information.pdf.