FDA approves trofinetide, now Daybue, as 1st treatment for Rett

New Acadia therapy expected to be available in US by end of April

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Acadia Pharmaceuticals’ trofinetide has become the first treatment to be approved by the U.S. Food and Drug Administration (FDA) for Rett syndrome. It will be marketed in the U.S. under the brand name Daybue, the company announced.

The medication is indicated for treating adults and children with Rett, ages 2 and older, Acadia said in a press release. The recommended dosage is twice daily, morning and evening, according to patient weight. The therapy can be given orally or via a feeding tube.

The newly approved treatment is expected to become commercially available by the end of April, according to the company. 

“This is a historic day for the Rett syndrome community and a meaningful moment for the patients and caregivers who have eagerly awaited the arrival of an approved treatment for this condition,” said Melissa Kennedy, CEO of the International Rett Syndrome Foundation, adding, “With today’s FDA decision, those impacted by Rett have a promising new treatment option that has demonstrated benefit across a variety of Rett symptoms, including those that impact the daily lives of those living with Rett and their loved ones.”

Acadia has a support program for U.S. patients starting and continuing on Daybue, and their caregivers. Called Acadia Connect, it offers personal assistance, financial resources, and prescription help. More information is available at AcadiaConnect.com or by calling 1-844-737-2223, weekdays, from 8 a.m. to 8 p.m. ET.

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Acadia filed for approval of trofinetide in 2022

On March 28, the company will hold an hourlong educational webinar, beginning at 7 p.m. ET, for caregivers to learn more about Daybue and Acadia Connect.

Daybue (trofinetide), formerly known as NNZ-2566, is a modified version of glypromate, a naturally occurring protein fragment that’s thought to reduce inflammation and support the health of synapses, the connections between nerve cells. Increased inflammation and reduced synapse function are both characteristic neurological abnormalities in Rett syndrome; the therapy aims to help normalize these processes in the brain.

Acadia applied for approval of trofinetide last year, and the FDA gave the application priority review, shortening that time period to six months from the usual 10. The FDA had previously awarded the therapy orphan drug, fast track, and rare pediatric disease status, each of which is designed to incentivize development and speed up the regulatory review process.

“As the first FDA-approved drug for the treatment of Rett syndrome, DAYBUE now offers the potential to make meaningful differences in the lives of patients and their families who have lacked options to treat the diverse and debilitating array of symptoms caused by Rett syndrome,” said Steve Davis, CEO of Acadia.

With the approval, the FDA granted Acadia a rare pediatric disease priority review voucher, which can be used for a faster review of a subsequent application of another treatment, or be transferred to another company.

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.

The application for Daybue’s approval was mainly supported by data from a Phase 3 clinical trial called LAVENDER (NCT04181723). That study enrolled 187 girls and young women with Rett syndrome, ages 5 to 20, who were given either trofinetide or a placebo for 12 weeks, or about three months. The therapy was administered twice daily as an oral solution; participants were given 30 to 60 mL based on their body weight.

Results showed that patients given trofinetide experienced an average reduction — representing an improvement — of more than five points on the Rett Syndrome Behaviour Questionnaire (RSBQ), a caregiver-measured assessment of Rett symptoms. The gains seen for patients on the therapy were significantly greater than those found among patients on the placebo, who improved by less than two points on average.

The strongest RSBQ score improvements for patients on trofinetide were related to fear, anxiety, body rocking, and blank facial expressions.

Significantly better scores with trofinetide versus the placebo also were seen with the Clinical Global Impression Scale-Improvement (CGI-I), a clinician-measured assessment of disease severity, and with a caregiver-assessed measure of communication ability called the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist – Social Composite Score (CSBS-DP-IT–Social).

Trofinetide treatment was generally well tolerated in the study. The most common side effects were diarrhea and vomiting, which were mostly mild to moderate in severity.

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Now Daybue, therapy is first to win FDA approval

The positive results from the FDA were met with excitement by the Rett community.

“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,” said Jeffrey L. Neul, MD, PhD, a professor at Vanderbilt University Medical Center and an investigator in LAVENDER.

“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,” Neul said.

Most of the participants who finished LAVENDER continued into an ongoing open-label extension study called LILAC (NCT04279314), in which all participants were treated with trofinetide and monitored for long-term safety and efficacy outcomes.

Acadia now is also conducting a clinical trial called DAFFODIL (NCT04988867), which is testing trofinetide in 15 girls, ages 2 to 5, with Rett syndrome. Results from DAFFODIL are expected later this year.

“Today marks an important milestone for the Rett community and Acadia,” Davis added. “We are grateful to all of the Rett syndrome patients, caregivers, clinical investigators and our employees who have contributed to making today a reality and look forward to getting DAYBUE to patients as quickly as possible.”