Discussing trofinetide data, FDA approval for Rett syndrome with Alan Percy, MD

Alan Percy, MD, Professor of Pediatrics, Neurology, Neurobiology, Genetics, and Psychology at the University of Alabama, Birmingham, and the lead author for the LILAC-1 and LILAC-2 studies, recently discussed significant advancements in the treatment of Rett syndrome, highlighting the FDA approval of trofinetide (Daybue; Acadia Pharmaceuticals), approved on March 13, 2023. Percy also discussed the recent long-term safety data for trofinetide, based on a pair of open-label extension studies LILAC-1 and LILAC-2.^1,2

"Actually, it's quite interesting that while there is great enthusiasm among parents of children, the survival in Rett syndrome is quite long. So average survival is over age 50. So, many adult women with Rett syndrome are also taking this medication," Percy explained, noting the trofinetide approval marked a significant milestone in the direct management of Rett syndrome symptoms.

Percy emphasized the groundbreaking nature of this treatment, noting that "this was the first product that was ever has been developed and approved by the FDA for direct treatment of the signs or symptoms of Rett syndrome. Other medications we use are for symptomatic care, but nothing has been available previously to direct at the basic underpinnings of Rett syndrome."

The pivotal trial for this treatment, known as the LAVENDER trial, was a "double-blind, placebo-controlled study lasting 12 weeks," Percy explained. The trial utilized the Rett Syndrome Behavioral Questionnaire (RSBQ) and the Clinical Global Impression of Improvement (CGI-I) as primary endpoints to measure the treatment's effectiveness. "What is quite remarkable is at the end of the first pivotal trial, 12 weeks both the RSBQ and the CGI-I showed improvement."

LILAC-1 was a 40-week, open-label extension of the LAVENDER trail and evaluated safety and efficacy of trofinetide in patients with Rett syndrome aged 5 to 21 years. LILAC-2 was a 32-month open-label extension evaluating trofinetide in females aged 5 to 22 years who had completed LILAC-1, according to Acadia Pharmaceuticals.¹

The most common side effects in the trials were diarrhea and vomiting.¹

Percy acknowledged that while the treatment shows significant promise, it is not without challenges. "I think it is important to mention that diarrhea can be a substantial problem, and there may be individuals who have to stop the treatment simply because the diarrhea is not manageable." However, he pointed out that strategies have been developed over time to manage this side effect more effectively. "We start at 50% of the recommended weight-based dose, and we gradually increase to the point of maximum tolerability."

References:

1. Clinical data from open-label extension LILAC-1 and LILAC-2 studies evaluating long-term safety and efficacy of Daybue (trofinetide) in patients with rett syndrome published in med. Acadia Pharmaceuticals. Press release. July 18, 2024. Accessed September 4, 2024. https://ir.acadia.com/news-releases/news-release-details/clinical-data-open-label-extension-lilac-1tm-and-lilac-2tm
2. FDA approves first treatment for Rett Syndrome. FDA. Press release. March 13, 2023. Accessed September 4, 2024. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-rett-syndrome