Trofinetide approved for Rett Syndrome from two years of age

15th March 2023

Trofinetide is approved for treatment of the rare, neuro-developmental disorder Rett Syndrome in patients from two years of age

Acadia Pharmaceuticals has announced that it has received approval for trofinetide as a treatment for adult and paediatric patients with Rett Syndrome from two years of age.

Rett syndrome is described as a neuro-developmental disorder characterised by typical early growth and development followed by a slowing of that development, loss of functional use of the hands, distinctive hand movements, slowed brain and head growth, problems with walking, seizures, and intellectual disability.

The condition primarily affects females resulting in severe cognitive and physical disabilities and is estimated to affect about 1 in 12,000 girls and is only rarely seen in boys. Virtually all patients with Rett syndrome have one of > 300 distinct loss-of-function mutations in the MECP2 gene on the X chromosome, which encodes methyl-CpG binding protein-2, an essential transcriptional regulator in the brain required for normal neurodevelopment.

Before trofinetide, which is given orally, there were no recognised treatments for Rett syndrome and the drug is believed to work by normalising aberrant neural function resulting from MECP2 mutations. In an exploratory phase 2, multicentre, double-blind, placebo-controlled, dose-escalation study, trofinetide was found to provide a clinically meaningful improvement for patients with the syndrome. The approval by the FDA was based on the findings from LAVENDER, a phase 3 study of trofinetide for Rett syndrome.

The LAVENDER study evaluated the efficacy and safety of trofinetide compared to placebo in 187 female patients with Rett syndrome, five to 20 years of age. In the study, treatment with trofinetide produced a statistically significant improvement (compared to placebo) on both co-primary efficacy endpoints, measured by the change from baseline, in Rett Syndrome Behaviour Questionnaire (RSBQ) total score (p = 0.018), which is a caregiver assessment on a range of disease symptoms, and the Clinical Global Impression-Improvement (CGI-I) scale score (p = 0.003) at week 12, which represents a physician-based assessment. In the study, the most common side effects were diarrhoea (82%) and vomiting (29%).

The drug is likely to be available in the US from April 2023 although no information on its release elsewhere is yet known.