Trofinetide for the Treatment of Rett Syndrome: Long-Term Safety and Efficacy Results from the Open-Label LILAC-2 Study
Abstract number :
2.45
Submission category :
11. Behavior/Neuropsychology/Language / 11B. Pediatrics
Year :
2023
Submission ID :
1337
Source :
www.aesnet.org
Presentation date :
12/3/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Ponni Subbiah, MD, MPH – Acadia Pharmaceuticals Inc.
Alan percy, MD – University of Alabama at Birmingham; Jeffrey nuel, MD – Vanderbilt Kennedy Center; Timothy Benke, MD – Children’s Hospital of Colorado/University of Colorado School of Medicine; Elizabeth Berry-Kravis, MD – Rush University Medical Center; Daniel Glaze, MD – Texas Children’s Hospital/Baylor College of Medicine; Eric Marsh, MD – Children’s Hospital of Philadelphia; Di An, PhD – Acadia Pharmaceuticals Inc.; kathie Bishop, PhD – Acadia Pharmaceuticals Inc.; James Youakim, MD – Acadia Pharmaceuticals Inc.
Rationale:
Trofinetide, a synthetic analog of glycine-proline-glutamate, was approved by the U.S. Food and Drug Administration in March 2023 for the treatment of Rett syndrome (RTT) in adults and pediatric patients aged ≥2 years. Trofinetide significantly improved core symptoms of RTT with an acceptable safety profile in the 12-week, randomized, placebo-controlled, phase 3 LAVENDER study (NCT04181723). Treatment with trofinetide continued to improve symptoms of RTT for up to 40 weeks, with a safety profile consistent with LAVENDER, in the phase 3, open-label LILAC study (NCT04279314). Here, we report the long-term safety and efficacy results of LILAC-2 (NCT04776746).
Methods:
Females with RTT, five to twenty-two years of age, who completed the LILAC study received open-label treatment with twice-daily, oral trofinetide for 32 months. Safety assessments included the incidence of adverse events (AEs). Efficacy endpoints included the caregiver-assessed Rett Syndrome Behaviour Questionnaire (RSBQ) and the clinician-assessed Clinical Global Impression–Improvement (CGI-I) scale.
Results:
In total, 77 participants were enrolled in LILAC-2. Of these, 41 and 36 participants were treated with trofinetide and placebo in LAVENDER, respectively. Overall, 79.2% of participants completed the study. The mean (standard error [SE]) duration of exposure to trofinetide for LILAC-2 participants, who were also participants of LAVENDER and LILAC, was 811.1 (23.16) and 692.3 (33.20) days for participants treated with trofinetide and placebo in LAVENDER, respectively. The most common AEs were diarrhea (53.2%), COVID-19 (27.3%), and vomiting (19.5%). The mean (SE) change in RSBQ total score from the LAVENDER baseline to Week 104 in LILAC-2 was −9.8 (3.38) and -13.8 (3.61) for participants treated with trofinetide and placebo in LAVENDER, respectively. Mean (SE) CGI-I scores compared with the LILAC baseline at Week 12 of LILAC-2 were 3.2 (0.14) and 3.0 (0.15) for patients treated with trofinetide and placebo in LAVENDER, respectively.
Conclusions:
Open-label treatment with trofinetide for up to 32 months in LILAC-2 continued to improve symptoms of RTT. The safety profile of trofinetide in LILAC-2 was consistent with the safety results of LAVENDER and LILAC.
Funding: Acadia Pharmaceuticals Inc.
Behavior