Last updated May 7, 2024, by Marisa Horak, MS
 Fact-checked by José Lopes, PhD
What is Daybue for Rett syndrome?
Daybue (trofinetide) is a daily treatment for Rett syndrome that can be taken by mouth or feeding tube. It was approved in the U.S. in March 2023, becoming the first therapy approved in the country for Rett syndrome.
The therapy was developed by Neuren Pharmaceuticals, which in 2018 licensed the rights in North America to Acadia Pharmaceuticals. The agreement was later expanded worldwide.
 How does Daybue work?
Daybue is broadly thought to reduce inflammation and promote the health of synapses, which are connections between nerve cells. Impaired synapse function and increased inflammation in the brain are both believed to contribute to abnormalities in Rett syndrome.
The active ingredient in Daybue is an analogue of glypromate (GPE), a protein fragment that’s naturally produced in the brain by the breakdown of IGF1 (insulin-like growth factor 1), a signaling molecule that plays important roles in coordinating brain development.
Who can use Daybue?
The U.S. Food and Drug Administration approved Daybue in March 2023 to treat Rett syndrome in adults and children at least 2 years old.
Who should not use Daybue?
There are no contraindications for using Daybue.
How is Daybue administered?
Daybue is a solution that is pink or red in color. Every 5 mL of the solution contains 1 gram of the active agent trofinetide.
The therapy should be taken twice daily, in the morning and evening. It may be taken by mouth or administered via a feeding tube, and can be taken with or without food.
If a dose is missed, the next dose should be taken as scheduled. Dosing should not be doubled. If a patient vomits shortly after taking Daybue, the next dose should be given as scheduled, but no additional dose should be given.
The dosage of Daybue varies according to body weight, as follows:
- For patients 9 kg to less than 12 kg (about 20 to 26 pounds), the dose is 25 mL twice per day.
- For those 12 kg to less than 20 kg (about 26 to 44 pounds), the dosage is 30 mL twice per day.
- For individuals 20 kg to less than 35 kg (about 44 to 77 pounds), the dose is 40 mL twice per day.
- For patients 35 kg to less than 50 kg (about 77 to 110 pounds), the dose is 50 mL twice per day.
- For individuals 50 kg (about 110 pounds) or more, the dosage is 60 mL twice per day.
Daybue in clinical trials
Phase 2 trials
Neuren conducted two Phase 2 studies with the main goal of assessing the safety profile of Daybue in patients with Rett syndrome. One trial enrolled 56 adults and adolescents with Rett, while the other study (NCT02715115) enrolled 82 Rett children, ages 5 to 15. In both studies, the participants were treated with various doses of the therapy or a placebo for a maximum of about one month.
The results from both trials indicated Daybue was generally well tolerated. The most common side effect was diarrhea and there were no serious side effects related to therapy. Measures of disease symptoms showed at least promising trends favoring Daybue over a placebo, providing a basis for further studies.
Phase 3 LAVENDER study
The FDA’s approval of Daybue was based on findings from the Phase 3 clinical trial LAVENDER (NCT04181723). The study, sponsored by Acadia, enrolled 187 girls and young women with Rett syndrome, ages 5-20. Participants were given Daybue, at a dose according to body weight, or a placebo for 12 weeks, or about three months.
The study’s main goal was to compare the effects of treatment on two standardized measures — the Rett Syndrome Behaviour Questionnaire (RSBQ), a caregiver-measured assessment of Rett symptoms, and the Clinical Global Impression Scale-Improvement (CGI-I), a clinician-based measure of overall health status.
The results showed that, after 12 weeks, the average decrease in RSBQ scores was significantly greater for patients on Daybue than a placebo, by 3.2 points on average, suggesting an improvement with the treatment. The greatest improvements were seen on scores related to fear, anxiety, body rocking, and blank facial expressions, according to data announced by Acadia.
Scores on the CGI-I also significantly favored Daybue over a placebo, by an average of 0.3 points. Based on CGI-I scores, 61% of patients on Daybue had no change in their clinical status, while 37.7% had at least minimal improvement and 1.3% had a minimally worse status. By comparison, for patients on a placebo, 81.4% had no change, 15.2% had at least minimal improvement, and 3.5% had minimal worsening.
Common side effects of Daybue
The most common side effects associated with Daybue in clinical trials were vomiting and diarrhea.
Diarrhea
Most patients have diarrhea during treatment with Daybue. If diarrhea occurs, healthcare providers should be notified so that appropriate treatments should be given and patients should increase the amount of fluids they’re drinking.
If diarrhea becomes severe or causes dehydration, Daybue may be stopped or paused, or the dose may be reduced.
The use of laxatives should be stopped before starting Daybue.
Weight loss
Some patients on Daybue experience a substantial amount of weight loss. Body weight should be monitored regularly for patients on the therapy.
If notable weight loss occurs, the treatment may be paused or discontinued, or the dose reduced.
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