Trofinetide for the treatment of Rett syndrome: Long-term safety and efficacy results of the 32-month, open-label LILAC-2 study.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Med Pub Date : 2024-10-11 Epub Date: 2024-07-17 DOI:10.1016/j.medj.2024.06.007

Alan K Percy, Jeffrey L Neul, Timothy A Benke, Elizabeth M Berry-Kravis, Daniel G Glaze, Eric D Marsh, Amy M Barrett, Di An, Kathie M Bishop, James M Youakim

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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.

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曲非奈德治疗雷特综合征：为期 32 个月的开放标签 LILAC-2 研究的长期安全性和有效性结果。

研究背景根据为期12周的随机3期LAVENDER研究结果，特罗非奈肽被批准用于治疗年龄≥2岁的雷特综合征（RTT）患者。在为期 40 周的 LILAC（LAVENDER 的开放标签扩展研究）中，特罗菲肽继续改善了 RTT 的症状，其安全性与 LAVENDER 相似。在此，我们报告为期32个月的开放标签延伸研究LILAC-2的长期安全性和疗效结果：方法：完成LILAC研究的5-22岁女性有资格参加LILAC-2研究。安全性和耐受性根据不良事件（AEs）的发生率进行评估。疗效通过雷特综合征行为问卷（RSBQ）和临床总体印象改善（CGI-I）评分进行评估。护理人员访谈探讨了患者在参与研究期间对雷特综合征的体验和特罗菲肽的疗效：LILAC-2共有77名参与者。最常见的AE为腹泻（53.2%）、COVID-19（27.3%）和呕吐（19.5%）。从LAVENDER基线到LILAC-2第104周，RSBQ评分的平均值（标准误差[SE]）变化为-11.8（2.45）。从 LILAC 基线到 LILAC-2 第 12 周，CGI-I 评分的平均值（标准误差 [SE]）为 3.1 (0.10)。大多数护理人员（96%；n = 24/25）对特罗芬肽的疗效表示满意或非常满意：结论：特罗芬肽的长期治疗可持续改善 RTT 症状，且不存在新的安全问题。照护者对特罗芬太尼的满意度与其对孩子和自己都有意义的改善有关：本研究得到了阿卡迪亚制药公司（美国加利福尼亚州圣迭戈）的支持。该研究已在 ClinicalTrials.gov：NCT04776746。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.