FDA Approves New Powder Formulation of Trofinetide for Enhanced Rett Syndrome Treatment Flexibility
核心洞察
The FDA has approved DAYBUE STIX (搜索), a dye- and preservative-free powder formulation of trofinetide that demonstrates bioequivalence to the original oral solution for treating Rett syndrome (搜索) in patients aged 2 years and older.
The new formulation can be mixed with water-based liquids, providing caregivers greater flexibility to customize dose volume and taste, particularly beneficial for pediatric patients and those with feeding challenges.
DAYBUE STIX (搜索) will be available on a limited basis beginning in the first quarter of 2026, with broader availability expected in early second quarter 2026, while the original oral solution remains available.
The FDA has approved trofinetide (DAYBUE STIX (搜索)) for oral solution, a powder formulation of trofinetide, for the treatment of Rett syndrome (搜索) in adult and pediatric patients aged 2 years and older. The dye- and preservative-free formulation is designed to provide greater flexibility in dose volume and taste while maintaining the same efficacy and safety profile as the approved oral solution.
DAYBUE is currently the first and only FDA-approved treatment for Rett syndrome (搜索). The newly approved formulation offers an alternative administration option while the original oral solution will remain available.
"DAYBUE, the first and only approved treatment for Rett syndrome (搜索), has provided thousands of patients with an important therapeutic option," said Catherine Owen Adams, Acadia's Chief Executive Officer. "With the approval of DAYBUE STIX (搜索), we are building on our commitment to turn scientific promise into meaningful innovation by introducing a new formulation informed by invaluable feedback from patients, caregivers, and health care providers."
Bioequivalence Data Support Regulatory Approval
According to Acadia, approval of trofinetide was informed by results from a bioequivalence study demonstrating that the powder formulation provides comparable systemic exposure to the original oral solution. This finding supports the expectation that patients receiving trofinetide will experience the same efficacy and safety outcomes established for trofinetide oral solution.
The efficacy and safety data supporting trofinetide were generated in the LAVENDER study, which evaluated trofinetide oral solution vs placebo in 187 girls and young women ages 5 to 20 years with Rett syndrome (搜索).
Results of the study demonstrated a statistically significant improvement over placebo on the co-primary endpoints. The co-primary endpoints included a change in baseline to 12 weeks in the Rett Syndrome (搜索) Behaviour Questionnaire (RSBQ) (P = 0.0175; effect size = 0.37) and the Clinical Global Impression-Improvement (CGI-I) scale score (P = 0.0030; effect size = 0.47) at 12 weeks.
The study also met its secondary endpoint, which was a change from baseline to week 12 in the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist–Social composite score (CSBS-DP-IT–Social) (P = 0.0064; effect size=0.43). This is a caregiver scale to evaluate the ability to communicate.
Because bioequivalence between the formulations was confirmed, additional efficacy trials were not required for the new powder formulation.
Enhanced Administration Flexibility for Patient 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 (搜索) and associate professor of Neurology at UCSF Benioff Children's Hospitals, Oakland. "DAYBUE STIX (搜索) 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."
Disease Background and Treatment Landscape
Rett syndrome (搜索) 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 6,000 to 9,000 individuals are affected. The disorder is most commonly caused by pathogenic variants in the MECP2 (搜索) 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 progressing to motor deterioration that may persist throughout adulthood. Most patients require lifelong supportive care.
Mechanism of Action and Safety Profile
Trofinetide is a synthetic analog of the N-terminal tripeptide of insulin-like growth factor 1 (搜索). The mechanism by which trofinetide exerts therapeutic effects in patients with Rett syndrome (搜索) 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 (搜索) deficiency.
DAYBUE and DAYBUE STIX (搜索) 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 (搜索) and an inhibitor of P-glycoprotein (搜索), and concomitant administration with sensitive CYP3A or P-glycoprotein substrates may increase the risk of adverse reactions.
Availability Timeline
Acadia reported that DAYBUE STIX (搜索) 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.