■为了评估EYP-1901的安全性和耐受性,一种含有vorolanib的玻璃体内插入物,pan-VEGF受体抑制剂包装在生物可侵蚀递送技术(DurasertE™)中,用于持续递送,在先前接受抗VEGF治疗的湿性年龄相关性黄斑变性(wAMD)患者中。
■第一阶段,多中心,prospective,开放标签,剂量递增试验。
■患有wAMD的患者和先前抗VEGF治疗反应的证据。
■患者接受单次玻璃体内注射EYP-1901。
■主要目的是评估EYP-1901的安全性和耐受性。次要目标评估了EYP-1901的生物活性,包括最佳矫正视力(BCVA)和中央子场厚度(CST)。探索性分析包括减少抗VEGF治疗负担和补充无注射率。
■参加440μg的17名患者(3名患者),1030μg(1名患者),2060μg(8名患者),和3090μg(5名患者)剂量组。无剂量限制性毒性,眼部严重不良事件(AE),或观察到与EYP-1901相关的全身性AE。没有证据表明与vorolanib或递送技术相关的眼部或全身毒性。中度眼部治疗引起的AE(TEAE)包括视敏度降低(2/17)和视网膜渗出(3/17)。一名BCVA降低的患者有3个分别减少17、18和16个字母,另一个只有25个字母。一个严重的TEAE,新生血管性AMD(即,恶化/进行性疾病活动),在17只研究眼睛中的1只报告,但被认为与治疗无关。在6个月和12个月时,BCVA从基线的平均变化为-1.8个字母和-5.4个字母。在6个月和12个月时,CST从基线的平均变化为+1.7μm和+2.4μm。在6个月和12个月时,治疗负担分别减少了74%和71%。在16只研究的眼睛中,13、8和5在3、6和12个月内不注射。
■在DAVIO试验中(ClinicalTrials.gov标识符,NCT04747197),EYP-1901具有良好的安全性,并且在先前治疗过的wAMD眼中具有良好的耐受性。在单次EYP-1901注射后,生物活性的测量保持相对稳定。这些初步数据支持正在进行的II期和计划中的III期试验,以评估疗效和安全性。
■作者对本文讨论的任何材料都没有专有或商业利益。
UNASSIGNED: To evaluate safety and tolerability of EYP-1901, an intravitreal insert containing vorolanib, a pan-VEGF receptor inhibitor packaged in a bioerodible delivery technology (Durasert E™) for sustained delivery, in patients with wet age-related macular degeneration (wAMD) previously treated with anti-VEGF therapy.
UNASSIGNED: Phase I, multicenter, prospective, open-label, dose-escalation trial.
UNASSIGNED: Patients with wAMD and evidence of prior anti-VEGF therapy response.
UNASSIGNED: Patients received a single intravitreal injection of EYP-1901.
UNASSIGNED: The primary objective was to evaluate safety and tolerability of EYP-1901. Secondary objectives assessed biologic activity of EYP-1901 including best-corrected visual acuity (BCVA) and central subfield thickness (CST). Exploratory analyses included reduction in anti-VEGF treatment burden and supplemental injection-free rates.
UNASSIGNED: Seventeen patients enrolled in the 440 μg (3 patients), 1030 μg (1 patient), 2060 μg (8 patients), and 3090 μg (5 patients) dose cohorts. No dose-limiting toxicity, ocular serious adverse events (AEs), or systemic AEs related to EYP-1901 were observed. There was no evidence of ocular or systemic toxicity related to vorolanib or the delivery technology. Moderate ocular treatment-emergent AEs (TEAEs) included reduced visual acuity (2/17) and retinal exudates (3/17). One patient with reduced BCVA had 3 separate reductions of 17, 18, and 16 letters, and another had a single drop of 25 letters. One severe TEAE, neovascular AMD (i.e., worsening/progressive disease activity), was reported in 1 of 17 study eyes but deemed unrelated to treatment. Mean change from baseline in BCVA was -1.8 letters and -5.4 letters at 6 and 12 months. Mean change from baseline in CST was +1.7 μm and +2.4 μm at 6 and 12 months. Reduction in treatment burden was 74% and 71% at 6 and 12 months. Of 16 study eyes, 13, 8, and 5 were injection-free up to 3, 6, and 12 months.
UNASSIGNED: In the DAVIO trial (ClinicalTrials.gov identifier, NCT04747197), EYP-1901 had a favorable safety profile and was well tolerated in previously treated eyes with wAMD. Measures of biologic activity remained relatively stable following a single EYP-1901 injection. These preliminary data support ongoing phase II and planned phase III trials to assess efficacy and safety.
UNASSIGNED: The author(s) have no proprietary or commercial interest in any materials discussed in this article.