Because bioequivalence between the formulations was confirmed, additional efficacy trials were not required for the new powder formulation.
Flexible administration may support individualized care
The powder formulation is designed to be mixed with water-based liquids, allowing caregivers to adjust dose volume and taste to better meet individual patient needs. This flexibility may be particularly relevant for pediatric patients and those with feeding challenges.
“The new formulation gives us an additional option for treatment with Daybue, allowing us to better customize care for our patients,” said Jennifer Martelle Tu, MD, PhD, director of Katie's Clinic for Rett Syndrome and associate professor of neurology at University of California San Francisco Benioff Children's Hospital Oakland. “Daybue Stix is a powder for oral solution that caregivers can mix with a variety of water-based liquids, providing flexibility to modify the taste and volume of their loved one's dose. We know that this kind of adaptability is something many Rett families have been seeking.”
Rett syndrome prevalence and clinical course
Rett syndrome is a rare neurodevelopmental disorder that primarily affects females and occurs in approximately 1 in 10,000 to 15,000 female births worldwide. In the United States, an estimated 6000 to 9000 individuals are affected. The disorder is most commonly caused by pathogenic variants in the MECP2 gene.
Patients typically experience a period of apparently typical early development followed by developmental stagnation and regression, including loss of purposeful hand use and communication skills. Many individuals later enter a plateau phase before their condition progresses to motor deterioration that may persist throughout adulthood. Most patients require lifelong supportive care.
Trofinetide mechanism of action
Trofinetide is a synthetic analogue of the N-terminal tripeptide of insulinlike growth factor 1. The mechanism by which trofinetide exerts therapeutic effects in patients with Rett syndrome is unknown. In animal studies, trofinetide has been shown to increase dendritic branching and synaptic plasticity signaling, findings that may be relevant to synaptic dysfunction associated with MECP2 deficiency.
Safety profile and clinical considerations for physicians
Daybue and Daybue Stix share the same approved indication and safety profile. In clinical studies, diarrhea was the most frequently reported adverse reaction, occurring in the majority of treated patients. Vomiting, fever, seizure, anxiety, decreased appetite, fatigue, and nasopharyngitis were also reported.
Clinicians are advised to monitor for persistent diarrhea, dehydration, vomiting-related aspiration risk, and clinically significant weight loss. Trofinetide is a weak inhibitor of CYP3A and an inhibitor of P-glycoprotein, and concomitant administration with sensitive CYP3A or P-glycoprotein substrates may increase the risk of adverse reactions.
Daybue Stix availability timeline
Acadia reported that Daybue Stix will be available on a limited basis beginning in the first quarter of 2026, with broader availability anticipated in the early second quarter of 2026. The existing oral solution formulation of Daybue will continue to be offered.
The pediatrician's role in prescribing trofinetide for Rett syndrome
