FDA Approves First Therapy for Rett Syndrome

Rare Daily Staff

The U.S. Food and Drug Administration approved Acadia Pharmaceutical’s Daybue for the treatment of the rare, neurodevelopmental disorder Rett syndrome, the first approved therapy for the condition.

The approval is for the treatment of Rett syndrome in adult and pediatric patients two years of age and older.

Rett syndrome is a complex condition caused by a genetic mutation on the MECP2 gene. It is characterized by a period of normal development until six to 18 months of age, followed by significant developmental regression with loss of acquired communication skills and purposeful hand use. Symptoms of Rett syndrome may also include development of hand stereotypies, such as hand wringing and clapping, and gait abnormalities.

Daybue is a synthetic version of a naturally occurring molecule known as the tripeptide glycine-prolineglutamate, which is part of a growth factor thought to support brain cells. The FDA approval of Daybue was supported by results from the pivotal phase 3 Lavender study evaluating the efficacy and safety of Daybue versus placebo in 187 female patients with Rett syndrome 5 to 20 years of age.

“Now, for the first time after decades of clinical research, healthcare providers finally have a treatment option to address a range of core behavioral, communication and physical symptoms for their patients living with Rett syndrome,” said Jeffrey Neul, professor of Pediatrics in the division of Neurology, Pharmacology, and Special Education at Vanderbilt University Medical Center and phase 3 Lavender study investigator.

In 2018, Acadia entered into an exclusive license agreement with Neuren Pharmaceuticals for the development and commercialization of Daybue for the treatment of Rett syndrome and other indications in North America. With the FDA approval of Daybue, Acadia has received a Rare Pediatric Disease Priority Review Voucher, which can be used to obtain priority review for a subsequent application. In January, Bluebird Bio sold its priority review voucher to Bristol Myers Squibb for $95 million.

The FDA approval of Daybue was supported by results from the pivotal phase 3 Lavender study evaluating the efficacy and safety of Daybue versus placebo in 187 female patients with Rett syndrome ages 5 to 20. In the study, treatment with Daybue demonstrated statistically significant improvement compared to placebo on both co-primary efficacy endpoints, as measured by the change from baseline in Rett Syndrome Behavior Questionnaire (RSBQ) total score and the Clinical Global Impression-Improvement (CGI-I) scale score at week 12.

The RSBQ is a caregiver assessment that evaluates a range of symptoms of Rett syndrome including vocalizations, facial expressions, eye gaze, hand movements (or stereotypies), repetitive behaviors, breathing, night-time behaviors, and mood. The CGI-I is a global physician assessment of whether a patient has improved or worsened.

In the study, the most common side effects were diarrhea (82 percent) and vomiting (29 percent).

Daybue is expected to be available in the United States by the end of April, 2023.

Photo: Jeffrey Neul, professor of Pediatrics in the division of Neurology, Pharmacology, and Special Education at Vanderbilt University Medical Center and phase 3 Lavender study investigator