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Trofinetide

The first FDA-approved treatment for Rett syndrome, a synthetic analogue of a naturally occurring IGF-1 tripeptide fragment.

StrongWell-Studied

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This information is for educational purposes. Peptide therapy should be guided by a licensed healthcare provider. Connect with a Noho clinician

What is Trofinetide?

Trofinetide is a synthetic analogue of glycine-proline-glutamate (GPE), the N-terminal tripeptide of IGF-1 that is naturally cleaved in the brain. It is the first and only FDA-approved treatment for Rett syndrome, a rare genetic neurological disorder. Trofinetide reduces neuroinflammation and supports synaptic function.

Why People Talk About It

First approved treatment for Rett syndrome

Strong

Neuroinflammation reduction

Moderate

Synaptic function support

Emerging

How It Works

Trofinetide is based on a brain-protective fragment naturally produced from IGF-1. It calms down brain inflammation and supports the connections between neurons, addressing core problems in Rett syndrome.

Common Questions

Safety Information

Important Safety Notes

Common Side Effects

Diarrhea (very common)VomitingWeight loss

Cautions

  • Monitor for dehydration from GI side effects
  • May require dose adjustment for weight changes
  • Only approved for Rett syndrome

What We Don't Know

Long-term effects beyond the clinical trial duration are being monitored.

Published Research

31 studies

Is trofinetide a future treatment for Rett syndrome? A comprehensive systematic review and meta-analysis of randomized controlled trials

Meta-AnalysisPMID: 39020317

Safety and efficacy of trofinetide in Rett syndrome: a systematic review and meta-analysis of randomized controlled trials

Meta-AnalysisPMID: 38521908

A meta-analysis of the efficacy and safety of trofinetide in patients with rett syndrome

Meta-AnalysisPMID: 38771525

Trofinetide for the treatment of Rett syndrome: Results from the open-label extension LILAC study

Randomized Controlled TrialPMID: 38917793

Trofinetide Treatment Demonstrates a Benefit Over Placebo for the Ability to Communicate in Rett Syndrome

Randomized Controlled TrialPMID: 38232652

A Phase 1, Open-Label Study to Evaluate the Effects of Food and Evening Dosing on the Pharmacokinetics of Oral Trofinetide in Healthy Adult Subjects

Randomized Controlled TrialPMID: 35622206

A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Fragile X Syndrome

Randomized Controlled TrialPMID: 32660869

Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome

Randomized Controlled TrialPMID: 30918097

A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Rett Syndrome

Randomized Controlled TrialPMID: 28964591

Population pharmacokinetics of NNZ-2566 in healthy subjects

Randomized Controlled TrialPMID: 28522374

Results from the phase 2/3 DAFFODIL study of trofinetide in girls aged 2-4 years with Rett syndrome

Phase III Clinical TrialPMID: 40043705

Exposure-Response Efficacy Modeling to Support Trofinetide Dosing in Individuals with Rett Syndrome

Phase III Clinical TrialPMID: 38363467

Managing Gastrointestinal Symptoms Resulting from Treatment with Trofinetide for Rett Syndrome: Caregiver and Nurse Perspectives

Phase III Clinical TrialPMID: 38378975

Physiologically-Based Pharmacokinetic Modeling of Trofinetide in Moderate Renal Impairment for Phase 1 Clinical Study Dose Selection with Model Validation

Phase I Clinical TrialPMID: 39516357

Characterization of the Pharmacokinetics and Mass Balance of a Single Oral Dose of Trofinetide in Healthy Male Subjects

Phase I Clinical TrialPMID: 38017349

Design and outcome measures of LAVENDER, a phase 3 study of trofinetide for Rett syndrome

Clinical TrialPMID: 35149233

Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study

Clinical TrialPMID: 37291210

Assessing Experiences With Trofinetide for Rett Syndrome: Interviews With Caregivers of Participants in Clinical Trials

Clinical TrialPMID: 39824747

Trofinetide for the treatment of Rett syndrome: Long-term safety and efficacy results of the 32-month, open-label LILAC-2 study

Clinical TrialPMID: 39025065

Profile of Trofinetide in the Treatment of Rett Syndrome: Design, Development and Potential Place in Therapy

ReviewPMID: 39525048

Recommendations for the management of gastrointestinal comorbidities with or without trofinetide use in Rett syndrome

ReviewPMID: 38869952

Trofinetide: First Approval

ReviewPMID: 37191913

Trofinetide for Rett Syndrome: Highlights on the Development and Related Inventions of the First USFDA-Approved Treatment for Rare Pediatric Unmet Medical Need

ReviewPMID: 37568516

Real-world benefits and tolerability of trofinetide for the treatment of Rett syndrome: The LOTUS study

PreclinicalPMID: 40936177

A Phase 1, Randomized, Open-Label Study to Assess the Bioequivalence of Trofinetide as a Ready-to-Use Oral Solution and Constituted Powder for Oral Solution in Healthy Adults

PreclinicalPMID: 41678137

Post-marketing safety concerns with trofinetide: a disproportionality analysis of the first therapeutic agent for Rett syndrome based on the FDA adverse event reporting system (FAERS)

PreclinicalPMID: 41613782

Trofinetide Improves Cognitive Function in APP/PS1 Mice by Suppressing Inflammation and Apoptosis

PreclinicalPMID: 41269410

Population Pharmacokinetics of Trofinetide in a Pediatric Population Aged 2-4 Years with Rett Syndrome

PreclinicalPMID: 39692837

Safety Profiles of Trofinetide in Pediatric Rett Syndrome Population: A Real-World Postmarketing Pharmacovigilance Analysis

PreclinicalPMID: 40849266

Trofinetide-Induced Enterocolitis Syndrome in a Child with Rett Syndrome

PreclinicalPMID: 41428727

Population Pharmacokinetic Modeling to Support Trofinetide Dosing for the Treatment of Rett Syndrome

PreclinicalPMID: 39692836

Always consult a qualified clinician

This information is for educational purposes. Peptide therapy should be guided by a licensed healthcare provider. Connect with a Noho clinician

Related Peptides

Quick Facts

Class
IGF-1 Tripeptide Analogue
Evidence
Strong
Safety
Well-Studied
Updated
Mar 2026
Citations
31PubMed

Also known as

DaybueNNZ-2566

Tags

FDA-ApprovedNeuroprotectiveRare Disease

Related Goals

Evidence Score

Overall Confidence80%

Clinical Trials

View Clinical Trials

Links to ClinicalTrials.gov for reference. Listing does not imply endorsement.

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