Trofinetide
Also known as: Daybue, Daybu (EU), NNZ-2566
A synthetic tripeptide analog of an IGF-1 fragment, FDA-approved in 2023 as Daybue for Rett syndrome. Prescription medication.
Last updated
Mechanism of Action
Trofinetide (glycyl-L-2-methylprolyl-L-glutamic acid) is a synthetic analog of glypromate (Gly-Pro-Glu), the N-terminal tripeptide cleaved from insulin-like growth factor 1 (IGF-1); the added methyl group on proline slows enzymatic breakdown and makes oral dosing practical. Its exact mechanism in Rett syndrome is not fully understood; preclinical work suggests it reduces neuroinflammation and microglial activation and supports synaptic structure and function. Neuren Pharmaceuticals first developed it as an intravenous neuroprotectant (NNZ-2566) for traumatic brain injury after its earlier glypromate program, then reformulated it orally for Rett and fragile X syndromes and licensed it to Acadia Pharmaceuticals.
- Half-life
- ~1.5 hours (oral)
- Administration Routes
- Oral
- Research Status
- Clinical
Reported Benefits
- FDA-approved treatment of Rett syndrome in patients aged 2 years and older
- Improved caregiver-rated Rett symptom scores versus placebo in the phase 3 LAVENDER trial
- Improved clinician-rated global impression scores in LAVENDER
- Studied in open-label extensions up to 32 months (LILAC, LILAC-2)
Potential Side Effects
- Diarrhea (very common; can lead to dehydration)
- Vomiting
- Weight loss
- Decreased appetite
- Fever, seizures and anxiety reported more often than with placebo
Common Dosing
Labeled dosing is an oral solution taken twice daily, morning and evening, with the dose set by body-weight band; it can be given by mouth or through a gastrostomy tube. Diarrhea management (such as stopping laxatives and adjusting fluids) is part of starting treatment. Dosing is set and supervised by the prescribing clinician.
The dosing information above is aggregated from research literature and anecdotal community reports for educational purposes only. It is not a recommendation, prescription, or medical advice. Peptides are sold as research chemicals only and are not intended for human use.
Contraindications
- Known hypersensitivity to trofinetide
- Not recommended in moderate or severe renal impairment
- Caution in patients at risk of dehydration or significant weight loss
No documented stacking partners for Trofinetide yet.
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Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study
2023
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Results from the phase 2/3 DAFFODIL study of trofinetide in girls aged 2-4 years with Rett syndrome
2025
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A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Fragile X Syndrome
2020
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NNZ-2566, a glypromate analog, improves functional recovery and attenuates apoptosis and inflammation in a rat model of penetrating ballistic-type brain injury
2009
Note: Preclinical rat study from the earlier intravenous NNZ-2566 brain-injury program.