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Study supported FDA and Health Canada approvals of DAYBUE for treatment of Rett syndrome in patients ages two years and older

—Results consistent with Phase 3 LAVENDER™ and open-label LILAC™ studies

SAN DIEGO—(BUSINESS WIRE)—Mar. 5, 2025—Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) today announced that the journal Med published results from the open-label study, DAFFODIL™, evaluating the safety, tolerability and exploratory efficacy of DAYBUE® (trofinetide) in girls ages two to four living with Rett syndrome (n = 15). The long-term Phase 2/3 study demonstrated DAYBUE had a similar safety profile in children two to four years of age as that observed in individuals with Rett syndrome five years of age and older in the 12-week LAVENDER™ study, and the 40-week LILAC-1™ and 32-month LILAC-2™ open-label extension studies. Results of all four studies supported the FDA approval of DAYBUE in adults and pediatric patients two years of age or older.

“Rett syndrome is a debilitating condition that often causes patients to lose acquired communication and motor skills starting as early as six to 18 months old which presents significant challenges for these children and their families,” said Alan Percy, M.D., Professor of Pediatrics, Neurology, Neurobiology, Genetics, and Psychology at University of Alabama, Birmingham and lead DAFFODIL author. “Outcomes from DAFFODIL further underscore trofinetide’s safety and tolerability across patient age groups and provide additional data to inform treatment plans and dosing for patients closer to the onset of symptoms.”

“The final DAFFODIL results provide critical insights into the safety and tolerability of DAYBUE in younger pediatric Rett syndrome patients, including effective strategies to mitigate common side effects of treatment,” said Ponni Subbiah, M.D., M.P.H., Acadia’s Senior Vice President, Global Head of Medical Affairs and Chief Medical Officer. “These findings, along with the caregiver exit interview feedback from the study, further our understanding of trofinetide’s role in managing this complex condition and the potential benefits of longer-term treatment.”

Diarrhea (80.0%) and vomiting (53.3%) were the most common treatment emergent adverse events (TEAEs), and all cases were of mild or moderate severity. Two participants discontinued the study early due to adverse events. The use of a diarrhea management plan, including discontinuation of laxatives and initiation of fiber, led to only one discontinuation due to diarrhea over the 78-week study. Serious TEAEs (n = 4) were considered unrelated to treatment.

The following exploratory efficacy endpoints supported symptom improvement:

Clinical Global Impression–Improvement (CGI-I) scale score (7-point scale where 1 is “very much improved” and 7 is “very much worse” was 3.3 ± 0.19 (mean ± standard error) at Week 4 and continued to improve to 2.2 ± 0.22 at Week 78.
Caregiver Global Impression–Improvement (CaGI-I) scale score (5-point scale where 1 is “much improved” and 5 is “much worse” at Week 12 (2.3 ± 0.12) and Week 78 (2.1 ± 0.31) indicated improvement compared with baseline.
Impact of Childhood Neurologic Disability-Quality of Life (ICND-QoL) scale (6-point scale where 1 is “poor” and 6 is “excellent” increased from baseline to Week 78 (3.9 ± 0.24 to 4.6 ± 0.31).
Caregivers (n = 7) who participated in the study exit interviews most frequently identified inability to communicate as the most impactful symptom of Rett syndrome (42.9%) and improved communication as the most desired treatment effect (71.4%). The most frequently reported improvements by caregivers during the exit interviews were in verbal communication (ability to say new words) (71.4%), improved eye contact (57.1%) and improved hand use (57.1%).


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