Trofinetide: evidence, FDA status and research

It is the first drug approved for Rett syndrome, a rare genetic brain illness. One trial of 187 people showed better scores than placebo, and four in five had diarrhea.

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Trofinetide is the first drug ever approved for Rett syndrome, a severe genetic neurological disorder affecting mostly girls.

Studies say

A single well-run phase 3 trial showed statistically significant improvement on caregiver and clinician rating scales, with diarrhea in four out of five patients, which earns an A for the approved indication.

Why grade A. Approval rests on LAVENDER, a 187-patient randomized placebo-controlled phase 3 trial that met both co-primary endpoints, preceded by two randomized phase 2 trials in 56 adolescents and adults and 82 children. The approved use matches the studied use, so it grades A, with the caveat that the endpoints are rating scales and the effect size is modest. ²³⁵⁶

FDA. Trofinetide is approved by the FDA as Daybue (March 2023) for the treatment of Rett syndrome in adults and children 2 years and older, the first drug approved for the condition. The current label on DailyMed (updated September 2026) also covers Daybue Stix, a powder for oral solution. ³⁴

Written from 6 cited sources. Fact-checked 2026-10-27: 24 claims checked, 13 corrected. Last refreshed 2026-10-27. Not physician reviewed.

What this means for you

What people take it for: Rett syndrome
Can a US doctor prescribe it?: Yes, FDA approved for Rett syndrome in people aged 2 and older.
Properly tested in people?: Yes, in large controlled trials. The main trial had 187 people.

Evidence checklist

Randomised controlled trial LAVENDER phase 3, placebo-controlledyes
Human study over 100 people LAVENDER, 187 patientsyes
More than one research group One phase 3 trial citedno information
Clinical outcomes, not surrogate markers Caregiver and clinician rating scalesno
Human safety data beyond case reports Extension studies; few hundred patientsyes

Drawn from the cited studies below. A dash means the sources give no information.

What it is

Trofinetide is a synthetic version of glycine-proline-glutamate, the three-amino-acid piece that is clipped from insulin-like growth factor 1 (IGF-1) in the brain. A methyl group added to the proline stops enzymes from destroying it, so it can be swallowed as a liquid. It was developed by Neuren Pharmaceuticals as NNZ-2566 and brought to approval by Acadia Pharmaceuticals. ²³⁶

Rett syndrome is caused by mutations in the MECP2 gene on the X chromosome. Girls develop normally for 6 to 18 months, then lose speech and purposeful hand use, and develop repetitive hand movements, breathing irregularities and seizures. Before 2023 treatment was symptomatic only. ²⁵

How it works

Trofinetide is an analog of glycine-proline-glutamate (GPE), the tripeptide at the start of the insulin-like growth factor 1 (IGF-1) protein, which the brain produces when IGF-1 is broken down. In Rett syndrome, synapses (the connections between neurons) fail to mature normally. The prescribing information states that the mechanism by which trofinetide works in Rett syndrome is unknown. ²⁴

What human research shows

LAVENDER randomized 187 girls and women aged 5 to 20 with Rett syndrome to trofinetide or placebo for 12 weeks. On the caregiver-rated Rett Syndrome Behaviour Questionnaire, scores improved by 4.9 points on trofinetide versus 1.7 on placebo. On the clinician-rated Clinical Global Impression-Improvement scale, mean scores were 3.5 versus 3.8 (lower is better), a difference that reached significance. A secondary communication measure also favored trofinetide. ²

Two phase 2 trials came first. In 56 adolescent and adult females with Rett syndrome, published in 2017, trofinetide was well tolerated and the higher of two doses met prespecified efficacy criteria. In 82 girls aged 5 to 15, published in 2019, the highest dose improved the Rett Syndrome Behaviour Questionnaire, a clinician-rated symptom scale and the Clinical Global Impression-Improvement score compared with placebo. A separate phase 2 trial in 72 adolescent and adult males with fragile X syndrome found the drug well tolerated, with an efficacy signal at the higher dose. Long-term open-label studies have followed patients for safety. ⁵⁶¹³

Study	Model	Finding
LAVENDER (Neul 2023)	Humans, n=187 females aged 5 to 20 with Rett syndrome, randomized placebo-controlled phase 3, 12 weeks	Both co-primary endpoints improved versus placebo: caregiver behavior questionnaire minus 4.9 versus minus 1.7, and clinician global impression 3.5 versus 3.8. ²
Pediatric phase 2 trial (Glaze 2019)	Humans, n=82 girls aged 5 to 15 with Rett syndrome, randomized double-blind placebo-controlled phase 2	The highest dose improved caregiver and clinician ratings, including the Rett Syndrome Behaviour Questionnaire and Clinical Global Impression-Improvement, over placebo. ⁶
Adolescent and adult phase 2 trial (Glaze 2017)	Humans, n=56 females with Rett syndrome, randomized double-blind placebo-controlled dose-escalation	Both doses were well tolerated and the higher dose met prespecified efficacy criteria. ⁵

Safety

Diarrhea was reported by 81 percent of trofinetide patients in LAVENDER versus 19 percent on placebo (82 versus 20 percent in the label's table), and vomiting by 29 percent versus 12 percent. Adverse reactions led 19 percent of treated patients to withdraw, diarrhea alone 15 percent. The label advises stopping laxatives before starting and managing diarrhea actively. Weight loss is the other listed warning. ²⁴

No new safety signals emerged in the extension studies, but experience is limited to 260 patients aged 2 to 40, and the phase 3 trial covered ages 5 to 20; use in children aged 2 to 4 is supported by pharmacokinetic and safety data in 13 patients, and use in adults relies largely on extrapolation. Long-term effects on growth and development are not yet characterized. ³⁴

Questions for your clinician

How large is the benefit on the rating scales, in practice?
How is diarrhoea managed?
What is known about safety in adults?

Questions people ask

Is trofinetide FDA-approved?

Yes. Daybue was approved in March 2023 for Rett syndrome in patients aged 2 and older. It was the first approved treatment for the disorder, and the current label also covers the Daybue Stix powder formulation. ³⁴

How much does trofinetide help?

In the 187-patient phase 3 trial, caregiver-rated behavior scores on a 45-item questionnaire improved by about 3 points more than placebo, and clinicians rated patients slightly more improved. These are statistically significant but modest changes; the drug does not reverse Rett syndrome. ²

What is the main side effect?

Diarrhea, in about 81 percent of patients during the phase 3 trial, with vomiting in about a quarter. About one in seven stopped because of it. Weight loss is the other labeled warning. ²⁴

How is it taken?

By mouth, as an oral solution or as Daybue Stix powder mixed into a solution, with the amount set by body weight in the prescribing information. It can also be given through a gastrostomy tube. ⁴

Citations

Berry-Kravis 2020, Pediatric Neurology: phase 2 trial of trofinetide in adolescent and adult males with fragile X syndrome doi.org
Neul 2023, Nature Medicine: Trofinetide for the treatment of Rett syndrome, phase 3 LAVENDER trial doi.org
FDA 2023: Daybue (trofinetide) approval label accessdata.fda.gov
DailyMed: Daybue (trofinetide) current prescribing information dailymed.nlm.nih.gov
Glaze 2017, Pediatric Neurology: double-blind randomized placebo-controlled phase 2 study of trofinetide in adolescent and adult females with Rett syndrome pubmed.ncbi.nlm.nih.gov
Glaze 2019, Neurology: double-blind randomized placebo-controlled phase 2 study of trofinetide in pediatric Rett syndrome pubmed.ncbi.nlm.nih.gov