People with Rett syndrome already have a safe and effective medication. Study data LAVENDERpublished today in “Nature Medicine”, show that the drug trofinetide achieves a significant improvement in symptoms.
These findings, based on data from a phase 3 trial, establish trofinetide as the first drug approved for the treatment of Rett syndrome.
Rett syndrome is a rare genetic disorder (caused by mutations in the MECP2 gene that result in a loss of function of the protein) that affects neurodevelopment, primarily in girls and women.
Symptoms of Rett syndrome include loss of verbal communication and fine and gross motor skills, along with behavior problems, seizures, and gastrointestinal problems.
With Rett Syndrome at first everything seems normal, but between 6 and 18 months of age it begins to regress. The girls stop talking, walking, sitting alone, picking up objects… They stop communicating with the rest of the environment. They do not follow their gaze, they do not interact, they seem to lose interest in their surroundings.
It is not a degenerative disorderbut of development, which will accompany them throughout their lives, making them completely dependent.
In Spain it affects just over 2,000 girls. It manifests itself in girls because the gene is located on the X chromosome, the effect is different depending on the chromosomal sex of the person. With the XY chromosome set, there is no working copy of the gene. Children often die during gestation or shortly after birth. But with a double X chromosome, the healthy copy partially compensates for the defect.
Until this drug, there was no effective treatment for the disorder.
Two previous phase 2 trials of trophinetidsa synthetic drug similar to the growth factor glycine-proline-glutamate found naturally in the brain, showed potential efficacy in reducing symptoms in small groups of patients with Rett syndrome.
The data now published in “Nature” are from the LAVENDER study, a phase 3 clinical trial, designed to determine the safety and efficacy of trofinetide treatment.
Until this drug, there was no effective treatment for the disorder.
Trofinetide has been approved by the US Food and Drug Administration (FDA) for the treatment of Rett syndrome in adult and pediatric patients. The drug, marketed under the name DAYBUE™, has been commercially available in the United States since the end of April 2023.
The team led by James Youakim, of Acadia Pharmaceuticals, randomly assigned 187 female patients with Rett syndrome to receive trofinetide or a placebo for 12 weeks.
To determine the efficacy of the treatment they used the Rett Syndrome Behavior Questionnaire (RSBQ) score, which is a caregiver-administered assessment that assesses a number of characteristics of Rett syndrome, including vocalizations, facial expressions, gaze, repetitive behaviors, breathing, nocturnal behaviors and mood.
They also used a physician global assessment (Clinical Global Impression-Improvement, CGI-I scale) to determine if the patient has improved or worsened.
The authors note that their results revealed significant improvements in both RSBQ scores and CGI-I scores, with no serious treatment-related adverse effects reported.
Youakim concludes that trofinetide it is relatively well tolerated and shows efficacy in improving key signs and symptoms associated with Rett syndrome.
At the moment the drug is only available in the US and its presentation to the European health authorities has not been announced.