Peptide

Trofinetide

Oral drug (solution) for Rett syndrome, a genetic neurodevelopmental disorder that almost always affects girls. It is the first approved treatment for this disease.

Regulatory status

Approved (FDA / EMA)

Family

Synthetic analog of the tripeptide GPE (derived from IGF-1)

Scientific evidence

Moderate

Number of findings

Where it acts

Brain and sleep

Also known as

trofinetide, NNZ-2566, Daybue, Daybu

Regulatory status

FDA (U.S.): Approved (2023, Daybue) for Rett syndrome in adults and children aged 2 years and older.

EMA (EU): Approved (2026, Daybu) for the neurobehavioral symptoms of Rett syndrome in adults and children aged 5 years and older.

Dose

Oral dose twice daily based on body weight (for example, from 5,000 mg to 12,000 mg twice daily depending on the weight band), per the label (FDA 2023). The regimen is always set by the specialist.

Safety

Diarrhea is very common (about 8 in 10 patients in the phase 3 trial) and can cause dehydration; also vomiting and weight loss. Weight and hydration must be monitored. Only with a prescription and specialist follow-up.

Interactions

It may increase exposure to drugs metabolized by CYP3A4 (such as midazolam). Caution with laxatives and other drugs that cause diarrhea.

Differences between women and men

Rett syndrome almost exclusively affects girls and women, so the phase 3 trial (LAVENDER) included only female patients; there are no efficacy data in males. View the study →

Effect by goal · level of evidence

Rett syndrome symptoms (phase 3 LAVENDER)

improves Moderate RCT (AA) in people

−4.9 vs −1.7 RSBQ

187 girls and women with Rett syndrome, 12 weeks. Trofinetide improved the RSBQ behavior scale more than placebo (−4.9 vs −1.7) and the clinical global impression (3.5 vs 3.8). The improvement is modest. Diarrhea occurred in 80.6% vs 19.1% with placebo.

View the study (RCT) →

Long-term efficacy and tolerability balance

improves Low-moderate review (A) in people

A 2024 review concludes that it improves the clinical global impression and some behavioral areas (mood, repetitive facial movements), but there is no demonstrated effect on epilepsy, heart, or bones. Diarrhea, vomiting, and weight loss are the main reasons for discontinuation.

View the study (review) →

In depth

Where it acts

Brain and sleep

How it works

It is a more stable version of the tripeptide GPE (glycine-proline-glutamate), which is released naturally when the growth factor IGF-1 is broken down. It is believed to modulate brain inflammation, synapse function and NMDA receptor activity. Its exact mechanism in Rett syndrome is not fully understood.

What the evidence says

In people

Rett syndrome symptoms (phase 3 LAVENDER). 187 girls and women with Rett syndrome, 12 weeks. Trofinetide improved the RSBQ behavior scale more than placebo (−4.9 versus −1.7) and the clinical global impression (3.5 versus 3.8). The improvement is modest. Diarrhea occurred in 80.6% versus 19.1% with placebo. PubMed 37291210
Long-term efficacy and tolerability balance. A 2024 review concludes that it improves the clinical global impression and some areas of behavior (mood, repetitive facial movements), but there is no demonstrated effect on epilepsy, heart or bones. Diarrhea, vomiting and weight loss are the main reasons for discontinuation. PubMed 39525048

Variants and related programs

Predecessor and related programs from Neuren: the origin is natural GPE (glypromate), tested in cardiac surgery without success. Trofinetide was first developed under the code NNZ-2566 for traumatic brain injury (phase 2 trial in the U.S., NCT00805818) and was also studied in phase 2 in fragile X syndrome, before focusing on Rett syndrome. Its successor, NNZ-2591 (another cyclic analog), is in trials for Phelan-McDermid, Angelman and Pitt-Hopkins syndromes; it is not approved.

References

Information, not medical advice. Prescription or unapproved peptides should only be used under medical supervision.