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
- Continued Improvements in RSBQ and CGI-I scores seen with long-term DAYBUE treatment in Phase 3 LAVENDER™ and LILAC studies
-- DAYBUE safety profile was consistent with findings from the LAVENDER trial
July 18, 2024 09:04 AM Eastern Daylight Time
SAN DIEGO--(BUSINESS WIRE)--Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) today announced that the journal Med published results from two open-label extension studies, LILAC-1™ and LILAC-2™, which showed that patients treated with DAYBUE™ who completed these studies experienced improvement in Rett symptoms as measured by the Rett Syndrome Behaviour Questionnaire (RSBQ). LILAC-1 was a 40-week, open-label extension study of the 12-week Phase 3 LAVENDER™ trial, evaluating the long-term safety and efficacy of DAYBUE in patients with Rett syndrome five to 21 years of age. LILAC-2 was a 32-month open-label extension study, evaluating the long-term safety and efficacy of DAYBUE in females aged five to 22 years who completed LILAC-1. The most common side effects reported in these studies were diarrhea and vomiting. Results from both studies also showed DAYBUE’s safety profile was consistent with results from the LAVENDER trial.
“These data from the open-label extension LILAC studies provide deeper insight into the long-term safety and potential benefit of DAYBUE for patients with Rett syndrome,” said Alan Percy, M.D., Professor of Pediatrics, Neurology, Neurobiology, Genetics, and Psychology at University of Alabama, Birmingham and lead author for the LILAC-1 and LILAC-2 studies. “These publications add to the growing body of research on clinical experience with DAYBUE and its potential ongoing impact for those living with this condition.”
“These findings from LILAC-1 and LILAC-2 add to the results from the pivotal Phase 3 LAVENDER trial and the ongoing LOTUS real-world evidence study and include patients who have been on treatment for over two years, contributing to a robust and growing portfolio of impactful data furthering our understanding of DAYBUE for the treatment of Rett syndrome,” said Ponni Subbiah, M.D., M.P.H., Acadia’s Senior Vice President, Global Head of Medical Affairs and Chief Medical Officer.
About the data:
In LILAC-1, 154 females with Rett syndrome five to 21 years of age received open-label treatment with DAYBUE for 40 weeks following double-blind treatment with DAYBUE (n = 69) or placebo (n = 85) in the 12-week LAVENDER study. The RSBQ mean (SE) change from LAVENDER baseline to week 40 in LILAC-1 was −7.3 (1.62) for participants who had been treated with DAYBUE in LAVENDER and completed the LILAC-1 study (N=44) and −7.0 (1.61) for participants who had been treated with placebo in LAVENDER and then were switched to DAYBUE in LILAC-1 and completed LILAC-1 (N=44). Changes from LAVENDER baseline to LILAC-1 week 40 for all RSBQ domain subscores were directionally in favor of DAYBUE regardless of treatment during LAVENDER, irrespective of age, baseline RSBQ severity or underlying MECP2 mutation severity. Mean (SE) Clinical Global Impression–Improvement (CGI-I) scores at week 40 compared to LILAC-1 baseline were 3.1 (0.11) and 3.2 (0.14) for participants who had been treated with DAYBUE or placebo in LAVENDER and completed the LILAC-1 study, respectively.
In the 32-month LILAC-2 study, 77 participants who completed LILAC-1 continued to receive open-label treatment with DAYBUE for up to an additional 104 weeks. Improvements in RSBQ scores were reported for participants treated with DAYBUE with a score decrease of ≥ 10% reported in 81.8% of participants at week 104. The mean (SE) change in RSBQ score from LAVENDER baseline to week 104 of LILAC-2 was −9.8 (3.38) for participants who had been treated with DAYBUE in LAVENDER and completed the LILAC-2 study (N=11), and −13.8 (3.61) for participants who received placebo in LAVENDER and completed the LILAC-2 study (N=11). The mean CGI-I from LILAC-1 baseline to Week 12 of LILAC-2 was 3.1 (0.10) for the overall population. 20.8% of patients had discontinued the study.
27 caregivers of 26 study participants took part in optional exit interviews to explore the patients’ experiences with Rett syndrome and DAYBUE during the trials. The most frequently reported improvements observed by caregivers to participants treated with DAYBUE in the studies were engagement with others (46.2%), hand use (42.3%), and eye gaze (30.8%). Caregivers also reported that some participants acquired new sounds (23.1%) or words (19.2%).
The safety profile of DAYBUE in LILAC-1 and LILAC-2 was consistent with the safety profile demonstrated in LAVENDER. The most common adverse events in LILAC-1 were diarrhea (74.7%) and vomiting (28.6%) with most reports of diarrhea as mild or moderate in severity and all reports of vomiting as mild or moderate in severity. In LILAC-2, the most common adverse events were diarrhea (53.2%), COVID-19 (27.3%), and vomiting (19.5%). The studies were conducted during the COVID pandemic. All reports of diarrhea were of mild or moderate severity and most reports of vomiting (93.3%) were mild or moderate in severity.
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