Clinical Data on Long-Term Safety and Efficacy of DAYBUE in Rett Syndrome Published

Acadia Pharmaceuticals Inc. recently announced publication in the journal Med of the results from their open-label extension studies, LILAC-1 and LILAC-2. These studies evaluated the long-term safety and efficacy of DAYBUE™ for individuals with Rett syndrome. The studies show promising improvements in Rett syndrome symptoms as measured by the Rett Syndrome Behaviour Questionnaire (RSBQ).

LILAC-1 was a 40-week study that extended the 12-week Phase 3 LAVENDER trial. This study focused on patients aged five to 21 years, assessing the long-term safety and efficacy of DAYBUE. LILAC-2, a 32-month study, continued to examine these aspects in females aged five to 22 years who had completed LILAC-1. The most frequently reported side effects in these studies were diarrhea and vomiting, consistent with the LAVENDER trial results.

Dr. Alan Percy, a professor at the University of Alabama, Birmingham, and the lead author of the studies, highlighted that these findings offer deeper insights into the long-term potential benefits of DAYBUE for patients with Rett syndrome. The studies provide additional evidence supporting DAYBUE's long-term impact on managing this condition.

Dr. Ponni Subbiah, Acadia’s Senior Vice President, emphasized that these findings contribute to a growing portfolio of data that enhances the understanding of DAYBUE's efficacy. The studies included patients who had been on treatment for over two years, adding to the robustness of the data.

In LILAC-1, 154 females with Rett syndrome aged five to 21 years received open-label treatment with DAYBUE for 40 weeks. Participants previously treated with DAYBUE in the LAVENDER trial showed a mean change in RSBQ score from the LAVENDER baseline to week 40 of -7.3. Those who had placebo in LAVENDER and switched to DAYBUE in LILAC-1 showed a mean change of -7.0. Improvements in RSBQ scores were noted regardless of age, baseline RSBQ severity, or MECP2 mutation severity.

In LILAC-2, 77 participants who completed LILAC-1 continued with DAYBUE treatment for an additional 104 weeks. At week 104, 81.8% of participants reported an RSBQ score decrease of 10% or more. For participants initially treated with DAYBUE in LAVENDER, the mean RSBQ score change was -9.8, while those who switched from placebo to DAYBUE showed a change of -13.8.

Exit interviews with 27 caregivers of 26 study participants revealed that the most observed improvements were in engagement with others (46.2%), hand use (42.3%), and eye gaze (30.8%). Some participants also acquired new sounds (23.1%) or words (19.2%).

The safety profile in both LILAC-1 and LILAC-2 was consistent with previous findings. In LILAC-1, the most common adverse events were diarrhea (74.7%) and vomiting (28.6%), most of which were mild or moderate. In LILAC-2, the main adverse events were diarrhea (53.2%), COVID-19 (27.3%), and vomiting (19.5%).

Rett syndrome is a rare neurodevelopmental disorder affecting 6,000 to 9,000 individuals in the U.S., typically caused by mutations in the MECP2 gene. Symptoms begin after an initial period of normal development and include loss of communication skills and hand use, with ongoing motor deterioration. DAYBUE, a synthetic analog of the N-terminal tripeptide of IGF-1, has shown promise in preclinical studies for increasing dendritic branching and synaptic plasticity.

Acadia Pharmaceuticals continues to advance breakthroughs in neuroscience, focusing on conditions like Prader-Willi syndrome, Alzheimer’s disease psychosis, and other neuropsychiatric symptoms. They have developed the only FDA-approved drugs for hallucinations and delusions associated with Parkinson’s disease psychosis and Rett syndrome.