Trofinetide
The first approved treatment for Rett syndrome, an oral analogue of an IGF-1 fragment
Trofinetide is a synthetic analogue of glycine-proline-glutamate, the first three amino acids of IGF-1. Approved as Daybue in March 2023, it is the first treatment for Rett syndrome, taken by mouth twice a day.
What is it?
Rett syndrome is a rare genetic neurodevelopmental disorder; the trials below enrolled girls and young women with it, from age 2 upward. Caregivers most often name communication as the ability they most want a treatment to help. Until 2023 there was no approved treatment for the disorder itself.
Trofinetide was built from a fragment of IGF-1: the tripeptide glycine-proline-glutamate, which in laboratory work affects how nerve connections function. In the 12-week phase 3 LAVENDER trial, 187 girls and young women with Rett syndrome received trofinetide or placebo; both co-primary measures, a caregiver behaviour questionnaire and a clinician's global rating, improved more on the drug, and so did a communication score. The FDA approved it as Daybue on March 10, 2023.
The effects were modest in size, and the main cost is gastrointestinal: diarrhoea affected about four in five patients in the trial. Its open-label extensions and a real-world study describe continued improvement and practical ways families manage the diarrhoea.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Half-Life: How Much Remains
The dataset records a half-life of about 1.5 hours (effective, oral, healthy subjects) for Trofinetide. After each half-life, half of what was in the circulation is gone, so about 3% remains after five. Real clearance varies with the person, the dose, the route and kidney or liver function; this is arithmetic on a published figure, not a dosing tool.
Published Research
The studies behind trofinetide, read from their PubMed abstracts.
LAVENDER phase 3, 187 patients
Over 12 weeks, the Rett Syndrome Behaviour Questionnaire improved by 4.9 points on trofinetide against 1.7 on placebo, and the clinician's global improvement score was 3.5 against 3.8 (lower is better); both co-primary end points were met, with effect sizes of 0.37 and 0.47. Diarrhoea affected 80.6% against 19.1%.
Communication in LAVENDER
A caregiver-rated communication score improved by 1.0 point more on trofinetide than placebo (effect size 0.43), and a clinician rating of non-verbal choice-making improved nominally; verbal communication did not change.
LILAC: 40-week extension
In 154 participants aged 5 to 21, behaviour scores improved by about 7 points from the original baseline by week 40; diarrhoea affected 74.7% and was the commonest reason for stopping (21.4%).
LILAC-2: 32 months
In 77 participants, behaviour scores had improved by 11.8 points from the original baseline at week 104; diarrhoea affected 53.2%, and 24 of 25 caregivers interviewed were satisfied with the benefits.
DAFFODIL: girls aged 2 to 4
In 15 young girls, weight-based dosing reached the target drug exposure; diarrhoea (80.0%) and vomiting (53.3%) were mostly mild or moderate, and clinician and caregiver ratings improved over about two years.
LOTUS: real-world use
Among 227 caregivers of patients prescribed trofinetide, 71% to 90% reported behavioural improvements over 12 months; doses were built up gradually, and diarrhoea was reported in 23% to 50% in the first weeks.
Side Effects & Contraindications
Reported Side Effects
From the studies above.
Contraindications & Cautions
Warnings from the Daybue label (DailyMed, effective September 4, 2026).
Legal Status
Trofinetide is approved in the US as Daybue.
Frequently Asked Questions
?What is trofinetide?
A synthetic analogue of glycine-proline-glutamate, a three-amino-acid fragment of IGF-1, approved as Daybue for Rett syndrome in patients aged 2 and older.
?How well does it work?
In the 12-week phase 3 LAVENDER trial, behaviour and global improvement scores improved more than on placebo, with modest effect sizes of about 0.4 to 0.5.
?What is the main side effect?
Diarrhoea, which affected 80.6% of patients on trofinetide in LAVENDER against 19.1% on placebo.
References
- [fda] US FDA, Drugs@FDA (openFDA): DAYBUE (trofinetide), NDA 217026, original approval March 10, 2023, prescription. Read October 3, 2026.
- [fda-pi] FDA. Daybue (trofinetide) oral solution US prescribing information (DailyMed set 67e6f2d9-21f6-466f-9def-826c6a4b8257, effective September 4, 2026). Read October 3, 2026.
- [clinical-trial] Neul JL, et al. "Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study." Nat Med, 2023;29(6):1468-1475. PMID: 37291210.
- [clinical-trial] Neul JL, et al. "Trofinetide Treatment Demonstrates a Benefit Over Placebo for the Ability to Communicate in Rett Syndrome." Pediatr Neurol, 2024;152:63-72. PMID: 38232652.
- [clinical-trial] Percy AK, et al. "Trofinetide for the treatment of Rett syndrome: Results from the open-label extension LILAC study." Med, 2024;5(9):1178-1189.e3. PMID: 38917793.
- [clinical-trial] Percy AK, et al. "Trofinetide for the treatment of Rett syndrome: Long-term safety and efficacy results of the 32-month, open-label LILAC-2 study." Med, 2024;5(10):1275-1281.e2. PMID: 39025065.
- [clinical-trial] Percy AK, et al. "Results from the phase 2/3 DAFFODIL study of trofinetide in girls aged 2-4 years with Rett syndrome." Med, 2025;6(6):100608. PMID: 40043705.
- [pubmed] Cosand L, et al. "Real-world benefits and tolerability of trofinetide for the treatment of Rett syndrome: The LOTUS study." Dev Med Child Neurol, 2026;68(3):407-417. PMID: 40936177.
Sources & Citations
Studies were read from their PubMed records; regulatory sources are listed below, read October 3, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.