DAYBUE (trofinetide CAS 853400-76-7) approved by the FDA, expected to be available at the end of next month.
Rett, commonly known as Rett syndrome, is one of the most common genetic causes of severe mental impairment in the world. It is an X-linked dominant condition that mostly affects girls and, in extremely rare occasions, boys. Rett's syndrome often manifests itself between the ages of 6 and 18 months. The majority of instances are caused by mutations in the CDKL5 and FOXG1 genes, in addition to the MECP2 gene. The underlying process is currently being explored, and there is no effective therapy. DAYBUE became the first and only medicine licensed in the United States for the treatment of Rett syndrome.
Acadia Pharmaceuticals Inc. reported on March 10, 2023 that the FDA has approved DAYBUE (trofinetide) for the treatment of Rett syndrome in adult and pediatric patients two years of age and older. It is expected to be available in the United States by the end of April 2023.
Trofinetide is a new IGF-1 amino-terminal tripeptide analogue that is being developed to treat the main symptoms of Rett syndrome by lowering neuroinflammation and promoting synaptic function. Trofinetide promotes synaptic maturation while also addressing synaptic and neuronal immaturity, both of which are pathophysiological characteristics of Rett syndrome. IGF-1 is largely generated by neurons and glial cells in the central nervous system, and it is essential for appropriate developmental activity, injury response, and illness. Trofinetide has been demonstrated to reduce inflammatory cytokine production, regulate microglia and astrocyte hyperactivation, and increase the number of accessible IGF-1 receptors that can bind to IGF-1.
Acadia received a rare pediatric illness priority review voucher with the FDA's approval of Daybue, which can be used to obtain priority review for subsequent applications. The FDA previously awarded trofinetide priority review, fast track status, orphan drug classification, and rare pediatric illness designation.
The major Phase 3 LAVENDER trial, which compared the effectiveness and safety of trofinetide vs placebo in 187 female Rett syndrome patients aged 5 to 20 years, provided support for DAYBUE approval.
The research evaluated the efficacy and safety of Daybue in female individuals with Rett syndrome aged 5 to 20 years. During 12 weeks, patients were randomly randomized to take trofinetide (n=93) or placebo (n=94) orally or through a gastrostomy tube.
The co-primary objectives were the change in Rett Syndrome Behavior Questionnaire (RSBQ) total score (caregiver evaluation) and Clinical Global Impression Improvement (CGI-I) score from baseline to week 12. (physician assessment). Lower scores indicate less severe Rett syndrome signs and symptoms.
The results of this research showed that DAYBUE treatment improved both co-primary efficacy endpoints compared to placebo, as measured by changes in Rett Syndrome Behavior Questionnaire (RSBQ) total scores (p=0.018) and Clinical General Impression Improvement (CGI-I) scale scores (p=0.003) at week 12 relative to baseline. The Rett Syndrome Behavior Questionnaire (RSBQ) is a caregiver evaluation that analyzes a variety of Rett syndrome symptoms such as vocalizations, facial expressions, eye gazing, hand motions (or stereotypes), repetitive activities, respiration, nocturnal behavior, and mood. The CGI-I is a worldwide physician evaluation that determines whether a patient's health has improved or deteriorated.
In terms of safety, the most common side effects reported in this research were diarrhea (82%), followed by vomiting (29%).
In terms of dosage, Daybue is a strawberry-flavored oral solution that contains 200 mg of tretinoin per mL. The dose is based on the patient's weight and can be given orally or through a gastrostomy tube.
Acadia Pharmaceuticals announces US FDA approval of Daybue™ (trofinetide) for the treatment of Rett syndrome in adult and pediatric patients two years of age and older. News release. Acadia Pharmaceuticals. March 10, 2023.
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