A potential first-of-its-kind drug to treat the symptoms of Rett syndrome received positive top-line results from a phase 3 trial sponsored by Acadia Pharmaceuticals Inc. and led by investigators from Vanderbilt University Medical Center to evaluate efficacy and safety.
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.
Currently, there are no FDA-approved medicines for the treatment of Rett syndrome.
The LavenderTM study 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," said Lavender study investigator Jeffrey Neul, MD, PhD, Annette Schaffer Eskind Professor and director of the Vanderbilt Kennedy Center. "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.
"A potential treatment for Rett syndrome is an important step forward in addressing this rare and serious neurological disease," said Neul, also a professor in the departments of Pediatrics, Neurology, Pharmacology and Special Education at Vanderbilt University Medical Center.
Rett syndrome, caused by mutations on the X chromosome gene MECP2, has 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, MD, assistant professor of Pediatrics in the Division of Pediatric Neurology at Monroe Carell Jr. Children's Hospital at Vanderbilt. "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 most common adverse events were diarrhea (80.6% with trofinetide vs. 19.1% with placebo), of which 97.3% in the trofinetide arm were characterized as mild-to-moderate, and vomiting (26.9% with trofinetide vs. 9.6% with placebo), of which 96% in the trofinetide arm were characterized as mild-to-moderate.
Serious adverse events were observed in 3.2% of study participants in both the trofinetide and placebo groups. Patients completing the Lavender study had the opportunity to continue to receive trofinetide in the open-label Lilac and Lilac-2 extension studies. More than 95% of participants who completed the Lavender study elected to roll-over to the Lilac open-label extension study.
The study results will be submitted for presentation at upcoming medical meetings.