Long-Term Data from LILAC-2 Study of Daybue for Rett Syndrome Reported

People who used Daybue (trofinetide; Acadia Pharmaceuticals, San Diego, CA) on a long-term basis showed improvements in the core symptoms of Rett syndrome, according to results of the 104-week LILAC-2 (NCT04776746) open-label extension (OLE) study. The safety profile results found in this OLE study were consistent with previously reported safety results from the 12-week LAVENDER (NCT04181723) phase 3 clinical trial and the 40-week LILAC (NCT04279314) OLE. These findings were presented at the 2023 American Epilepsy Society (AES) annual meeting.

LILAC-2 enrolled 77 female participants with Rett syndrome who previously participated in LAVENDER and LILAC and were able to receive Daybue as an ingestible oral solution or by gastronomy tube. Participants received Daybue twice daily at a weight-based dose for 32 months (104 weeks) to assess for long-term safety and efficacy. Rett Syndrome Behaviour Questionnaire (RSBQ) and Clinical Global Impression–Improvement (CGI-I) scores were assessed as efficacy endpoints, and long-term safety and tolerability were assessed by documenting the  incidence of adverse events (AEs), including new treatment-emergent adverse events (TEAEs) and AEs that began during LAVENDER and LILAC and continued through baseline of LILAC-2.

In terms of results:

• From baseline to week 104, the mean change in RSBQ total score was -9.8 (standard error [SE]: 3.38) for participants who originally received Daybue in LAVENDER, and -13.8 (SE: 3.61) for participants who originally received placebo in LAVENDER.
• The mean change in RSBQ score for the total LILAC-2 group was -11.8 (SE: 2.45).
• From baseline to week 12, the mean CGI-I scores were 3.2 (SE: 0.14) and 3.0 (SE: 0.15), respectively, for participants who originally received Daybue and placebo in LAVENDER.
• The LILAC-2 CGI-I score for the total group was 3.1 (0.10).

The most common AEs in the total population were diarrhea (53.2%), COVID-19 (27.3%), and vomiting (19.5%), with 20.8% of participants discontinuing during the study. Five participants discontinued due to AEs, 4 due to death (not considered to be related to the study drug), 3 due to lack of efficacy, and 2 due to other reasons.

The study was supported by Acadia Pharmaceuticals.