By Counterforce Health Team —

Understanding Daybue (Trofinetide): The First Approved Treatment for Rett Syndrome

Rett syndrome is a rare and challenging neurological disorder that primarily affects girls. For decades, families and clinicians have managed symptoms without a disease-specific treatment. That changed in 2023 with the approval of Daybue® (trofinetide) — the first medication specifically developed and approved for Rett syndrome.

This breakthrough represents a major step forward in care for individuals living with the condition.

What Is Daybue?

Daybue (generic name trofinetide) is a prescription medication approved for the treatment of Rett syndrome in children aged 2 years and older and adults. It was developed to target some of the underlying biological mechanisms of the disorder rather than simply managing symptoms.

Daybue is supplied as an oral liquid solution (200 mg/mL) and is taken twice daily, either by mouth or through a feeding tube.

Understanding Rett Syndrome

Rett syndrome is a rare genetic neurodevelopmental disorder caused most often by mutations in the MECP2 gene. It primarily affects girls, although boys can rarely be affected as well.

Children with Rett syndrome typically develop normally for the first 6 to 18 months of life, then begin to lose skills such as purposeful hand use, communication, and coordination. Other features can include breathing irregularities, seizures, scoliosis, and significant motor impairments.

Because it is caused by a genetic mutation, Rett syndrome affects how nerve cells communicate and how the brain develops over time.

How Daybue Works

The exact mechanism of action of Daybue in Rett syndrome is not fully understood. However, trofinetide is a synthetic version of a naturally occurring fragment of insulin-like growth factor 1 (IGF-1) — a protein involved in brain development and function.

Preclinical studies suggest that trofinetide may help improve the way brain cells communicate, enhance synaptic function, and reduce inflammation in the nervous system. This could help improve some of the symptoms seen in Rett syndrome.

Clinical Studies and Approval

Daybue was approved by the U.S. Food and Drug Administration (FDA) in March 2023 after successful clinical trials. The pivotal study included children and young adults with Rett syndrome and compared Daybue to placebo over 12 weeks.

Participants who received Daybue showed statistically significant improvement in:

  • Behavioral symptoms as measured by the Rett Syndrome Behavior Questionnaire (RSBQ)
  • Overall clinical condition as rated by clinicians on the Clinical Global Impression–Improvement (CGI-I) scale

While Daybue is not a cure, these improvements were meaningful for patients and families, marking the first targeted therapy for Rett syndrome.

How Daybue Is Taken

  • Form: Oral solution, 200 mg/mL
  • Administration: Twice daily, morning and evening
  • Route: By mouth or via gastrostomy (G-tube)
  • Dosing: Based on body weight; your healthcare provider will calculate the exact dose
  • Storage: Refrigerate upright; discard 14 days after opening

Daybue can be taken with or without food. If gastrointestinal side effects occur, your provider may suggest taking it with meals or adjusting timing.

Benefits of Daybue

Daybue is the first and only FDA-approved treatment that directly targets the biology of Rett syndrome. Potential benefits may include:

  • Improved communication and interaction
  • Reduced severity of behavioral and motor symptoms
  • Better overall daily functioning
  • Enhanced quality of life for patients and families

Not every individual will respond the same way, but even modest improvements can make a significant difference in daily life and caregiving.

Possible Side Effects

Like all medications, Daybue can cause side effects. The most common include:

  • Diarrhea
  • Vomiting
  • Decreased appetite
  • Weight loss
  • Fatigue or sleep changes
  • Fever

Diarrhea and weight loss were the most frequent reasons patients required dose adjustments or additional support. Careful monitoring of hydration, nutrition, and weight is important, especially in the first few weeks of treatment.

Patients should not use laxatives while taking Daybue unless directed by their doctor.

Precautions

Daybue may not be appropriate for everyone. Important precautions include:

  • Kidney function: Use is not recommended in individuals with moderate to severe renal impairment.
  • Dehydration risk: Because of diarrhea and vomiting risk, maintain adequate hydration.
  • Drug interactions: Daybue may affect how other medications are processed in the body. Always inform your provider about all medicines and supplements being used.

Your healthcare provider will review your child’s health history, current medications, and overall condition before starting Daybue.

Support for Families

Managing Rett syndrome is a team effort involving physicians, therapists, dietitians, and caregivers. Adding Daybue to the care plan may require adjustments in routines and close follow-up with the healthcare team.

Families are encouraged to:

  • Keep a daily symptom and side effect log
  • Monitor weight and hydration regularly
  • Store medication correctly in the refrigerator
  • Maintain open communication with healthcare providers about any concerns

Support programs from the manufacturer and Rett syndrome foundations can help with education, access, and financial assistance.

The Bottom Line

Daybue (trofinetide) represents a historic milestone in the treatment of Rett syndrome — the first therapy approved to address the underlying biology of this devastating condition.

While it does not cure Rett syndrome, Daybue offers new hope for improved quality of life and daily functioning for patients and their families. Ongoing research will continue to refine how it is used and who benefits most.

If you care for someone with Rett syndrome, speak with a neurologist or developmental specialist to learn whether Daybue may be a suitable option.