Trofinetide for the treatment of Rett syndrome: Long-term safety and efficacy results of the 32-month, open-label LILAC-2 study
- PMID: 39025065
- DOI: 10.1016/j.medj.2024.06.007
Trofinetide for the treatment of Rett syndrome: Long-term safety and efficacy results of the 32-month, open-label LILAC-2 study
Abstract
Background: Trofinetide was approved for the treatment of Rett syndrome (RTT) in patients aged ≥2 years based on the results of the 12-week, randomized, phase 3 LAVENDER study. In LILAC, a 40-week, open-label extension study of LAVENDER, trofinetide continued to improve the symptoms of RTT, with a similar safety profile as LAVENDER. Here, we report long-term safety and efficacy results of LILAC-2, a 32-month, open-label extension study.
Methods: Females aged 5-22 years who completed LILAC were eligible to enter LILAC-2. Safety and tolerability were assessed with the incidence of adverse events (AEs). Efficacy was assessed with Rett Syndrome Behaviour Questionnaire (RSBQ) and Clinical Global Impression-Improvement (CGI-I) scores. Caregiver interviews explored the patient's experience with RTT and the efficacy of trofinetide during study participation.
Findings: In total, 77 participants were enrolled in LILAC-2. The most common AEs were diarrhea (53.2%), COVID-19 (27.3%), and vomiting (19.5%). The mean (standard error [SE]) change in RSBQ score from LAVENDER baseline to week 104 of LILAC-2 was -11.8 (2.45). The mean (SE) CGI-I score from LILAC baseline to week 12 of LILAC-2 was 3.1 (0.10). Most caregivers (96%; n = 24/25) were satisfied or very satisfied with the benefits of trofinetide.
Conclusions: Long-term treatment with trofinetide continued to improve RTT symptoms, without new safety concerns. Caregivers reported satisfaction with trofinetide related to improvements that were meaningful for their child and themselves.
Funding: The study was supported by Acadia Pharmaceuticals (San Diego, CA, USA). This study was registered at ClinicalTrials.gov: NCT04776746.
Keywords: LILAC-2 study; Rett syndrome; Translation to patients; open-label extension; trofinetide.
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests A.K.P. is co-editor of Translational Science of Rare Diseases, received research funding from the National Institutes of Health, and is a consultant for Acadia Pharmaceuticals, Anavex Life Sciences, AveXis, and GW Pharmaceuticals, as well as advisor to the International Rett Syndrome Foundation. J.L.N. has received research funding from the International Rett Syndrome Foundation, the National Institutes of Health, and the Rett Syndrome Research Trust; has received personal consultancy fees from Acadia Pharmaceuticals, Analysis Group, AveXis, F. Hoffmann-La Roche, GW Pharmaceuticals, Myrtelle, Neurogene, Newron Pharmaceuticals, Signant Health, and Taysha Gene Therapies; has received personal consultancy fees for the preparation of CME activities for Medscape and the Peer Review Institute; serves on the scientific advisory board of Alcyone Therapeutics; is a scientific co-founder of LizarBio Therapeutics; and was a member of a data safety monitoring board for clinical trials conducted by Ovid Therapeutics. T.A.B. has received research funding from the GRIN2B Foundation, the International Foundation for CDKL5 Research, the Loulou Foundation, the National Institutes of Health, and the Simons Foundation; has received consultancy fees from Alcyone Therapeutics, GRIN Therapeutics, the International Rett Syndrome Foundation, Marinus Pharmaceuticals, Neurogene, Takeda, Taysha Gene Therapies, Ultragenyx, and Zogenix/UCB Pharma; and has participated in clinical trials with Acadia Pharmaceuticals, GW Pharmaceuticals, Marinus Pharmaceuticals, Ovid Therapeutics, and Rett Syndrome Research Trust; all remuneration has been made to his department. E.M.B.-K. has received funding from Acadia Pharmaceuticals, Alcobra, AMO Pharma, Asuragen, AveXis, Biogen, BioMarin, Cydan Development, EryDel, ESCAPE Bio, Fulcrum Therapeutics, GeneTx, GW Pharmaceuticals, Healx, Ionis Pharmaceuticals, Jaguar Health, Lumos Pharma, Marinus Pharmaceuticals, Neuren Pharmaceuticals, Neurogene, Neurotrope, Novartis, Orphazyme, Ovid Therapeutics, REGENXBIO, Retrophin, Roche, Seaside Therapeutics, Taysha Gene Therapies, Tetra Therapeutics, Ultragenyx, Vtesse/Sucampo/Mallinckrodt Pharmaceuticals, Yamo Pharmaceuticals, and Zynerba Pharmaceuticals to consult on trial design or run clinical or lab validation trials in genetic neurodevelopmental or neurodegenerative disorders, all of which have been directed to Rush University Medical Center in support of rare disease programs. D.G.G. has received personal compensation and research support from Acadia Pharmaceuticals, Neuren Pharmaceuticals, and Newron Pharmaceuticals. E.D.M. has received research support from the Eagles Autism Foundation, the International CDKL5 Research Foundation, the International Rett Syndrome Foundation, the Loulou Foundation, the National Institute of Child Health and Human Development, the National Institute of Neurological Disorders and Stroke, the Penn Orphan Disease Center, and the Rett Syndrome Research Trust; has been a site principal investigator for trials from Acadia Pharmaceuticals, GW Pharmaceuticals, Marinus Pharmaceuticals, Stoke Therapeutics, Takeda, and Zogenix; and has received personal compensation for consulting from Acadia Pharmaceuticals and Stoke Therapeutics. A.M.B. is an employee of RTI Health Solutions, which received funding from Acadia Pharmaceuticals for the design, conduct, and analysis of the qualitative interviews. D.A. and J.M.Y. are employees of and stakeholders in Acadia Pharmaceuticals. K.M.B. was an employee of Acadia Pharmaceuticals while LILAC-2 was conducted.
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