Rett Syndrome Drug Studied at Vanderbilt Kennedy Center (TN IDDRC, UCEDD, LEND) Approved for Patients

July 19, 2023

A headshot of Dr. Jeffrey Neul, a smiling white man with short red hair, a beard, and glasses, wearing a black suit jacket, white button-down shirt, and peach tie.
A headshot of Dr. Jeffrey Neul, a smiling white man with short red hair, a beard, and glasses, wearing a black suit jacket, white button-down shirt, and peach tie.

AUCD's network of Intellectual and Developmental Disability Research Centers (IDDRCs) consists of 16 Centers. Fifteen Centers currently receive funding from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD). IDDRCs contribute to the development and implementation of evidence-based practices by evaluating the effectiveness of biological, biochemical, and behavioral interventions; developing assistive technologies; and advancing prenatal diagnosis and newborn screening.

The first drug to treat the symptoms of Rett syndrome was recently approved, following a Nature Medicine study publishing results from the pivotal phase 3 LAVENDER study led by investigators from the Vanderbilt Kennedy Center (TN IDDRC, UCEDD, LEND)  to evaluate efficacy and safety of trofinetide.

Positive findings from the study were integral to the Food and Drug Administration’s (FDA) approval of the drug in March for the treatment of Rett syndrome in adults and children 2 years of age and older. It is taken twice daily either orally or via gastrostomy tube.

Rett syndrome, which impacts 6,000 to 9,000 U.S. patients and occurs in approximately 1 of every 10,000 to 15,000 female births worldwide, is a rare, debilitating neurological disorder that occurs primarily in females following apparently normal development for the first six months of life. It is often misdiagnosed as autism, cerebral palsy or non-specific developmental delay.

“The LAVENDER study was designed to measure the effect of trofinetide treatment on the range of behavioral, communication and physical Rett syndrome symptoms that significantly impact the quality of life for patients and their loved ones,” said study lead author Jeffrey Neul, M.D., Ph.D., Annette Schaffer Eskind Professor and director of the Vanderbilt Kennedy Center (VKC).

“The publication of the efficacy and safety results for trofinetide reinforces the significance of this study as a critical advancement in Rett syndrome research, furthering our ability to treat this devastating disease,” he said. “It is quite exciting that now there is an FDA-approved drug for this rare neurodevelopmental disorder, which is a first for such neurodevelopmental disorders in general. Hopefully, the success of this phase 3 trial helps support further clinical development of novel therapies for Rett syndrome and other severe neurodevelopmental disorders.”

LAVENDER was a phase 3, 12-week, double-blind, randomized, placebo-controlled study of the drug trofinetide in 187 young females, ages 5 to 20, with Rett syndrome.

Trofinetide met co-primary efficacy endpoints demonstrating statistically significant improvement over placebo in the Rett Syndrome Behaviour Questionnaire, a caregiver assessment of the core symptoms of Rett syndrome, and the Clinical Global Impression of Improvement, a physician assessment of illness improvement or worsening relative to baseline.

It also met its key secondary endpoint, demonstrating a statistically significant separation over placebo in the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist–Social composite score.

“These are encouraging results for patients and families affected by Rett syndrome,” Neul said. “Patients reported improvements in core symptoms, like being able to respond to a choice when asked by their parents, or experiencing more freedom from the repetitive hand movements that create obstacles in other areas of their lives.”

Rett syndrome, caused by mutations on the X chromosome gene MECP2has symptoms typically presenting between 6 to 18 months of age, including loss of purposeful hand use (fine motor skills), repetitive hand movements, absent or impaired mobility (gross motor skills), loss of communication skills (including eye contact) and inability to independently conduct activities of daily living.

Symptoms also include seizures, disorganized breathing patterns, an abnormal side-to-side curvature of the spine (scoliosis) and sleep disturbances.

“The symptoms of Rett syndrome impact all aspects of an individual’s daily life and take a profound emotional toll on families,” said Cary Fu, M.D., assistant professor of Pediatrics in the Division of Pediatric Neurology at Monroe Carell Jr. Children’s Hospital at Vanderbilt and VKC researcher. “I am encouraged by the trial results and hopeful that we will finally have an effective means of modifying the core symptoms and improving quality of life for families with Rett syndrome.”

The phase 3 trial for Trofinetide was sponsored by Acadia Pharmaceuticals Inc.