FDA Approves First Treatment for Rett syndrome

The FDA has okayed the first and only drug approved to treat the rare disease Rett syndrome. Acadia Pharmaceuticals’ Daybue (trofinetide) is approved for both adult and pediatric patients two years of age and older with the disease. Daybue is expected to be available in the United States by the end of April.

Rett syndrome is a neurodevelopmental disorder that affects mostly girls and is caused by mutations on the X chromosome on a gene called MECP2. Children experience normal early growth followed by slowing of development. Gradually, mental and physical symptoms appear, causing progressive loss of motor skills and the ability to communicate. The incidence in the United States is one in 10,000 girls.

Daybue is a novel synthetic analog of the amino‐terminal tripeptide of IGF-1 that is thought to stimulate synaptic maturation. In the central nervous system, IGF-1 is produced by both of the major types of brain cells – neurons and glia. Daybue has been shown to inhibit the production of inflammatory cytokines, inhibit the overactivation of microglia and astrocytes, and increase the amount of available IGF-1 that can bind to IGF-1 receptors.

Brendan Teehan

The list price of Daybue will be $21.10 per milliliter, or an estimated average net realized cost to payors of about $375,000 annually, Brendan Teehan, executive vice president, chief operating officer and head of commercial at Acadia, told Formulary Watch. Acadia’s national account managers will work closely with payer formulary and clinical managers to assure patients with Rett syndrome have access to the first therapy to treat the underlying neurodevelopmental aspect of their disease, according to Teehan.

Patients take Daybue either orally or via gastrostomy tube, the FDA said. The recommended dose is based on patient weight and Daybue is taken twice daily, with or without food.

There are an estimated 6,000 to 9,000 people living with Rett syndrome in the United States, according to Teehan. “Most patients living with Rett syndrome will live into adulthood and require round-the-clock care,” he said.

The Acadia Connect support program will offer personal assistance, financial resources and prescription support to patients and caregivers starting and continuing appropriate Daybue therapy. Each dedicated support team includes a nurse care coordinator, a family access manager and 24/7 clinical pharmacist support, according to Acadia.

“Rett syndrome is a profoundly debilitating and complex, rare, neurodevelopmental disorder that presents differently across patients and can lead to an array of unpredictable symptoms throughout the course of a patient’s life,” Jeffrey L. Neul, M.D., Ph.D., Annette Schaffer Eskind Chair and directorat the Vanderbilt Kennedy Center, professor of pediatrics at Vanderbilt University Medical Center, and phase 3 LAVENDER study investigator, said in a press release.

The FDA approval of Daybue was supported by results from the pivotal phase 3 LAVENDER study evaluating the efficacy and safety of trofinetide versus placebo in 187 female patients with Rett syndrome five to 20 years of age. Daybue demonstrated statistically significant improvement compared with 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 scale score at week 12.

Most common adverse reactions, occurring in at least 10% of Daybue-treated patients and twice the rate of placebo, included diarrhea (81%) and vomiting (27%).

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 2018, Acadia entered into an exclusive license agreement with Neuren Pharmaceuticals to develop and commercialize trofinetide for the treatment of Rett syndrome and other indications in North America.