Department of Ophthalmology, Duke University, Durham, North Carolina.
IVERIC bio, Inc., New York, New York.
Ophthalmology. 2021 Apr;128(4):576-586. doi: 10.1016/j.ophtha.2020.08.027. Epub 2020 Sep 1.
The complement pathway may play a key role in the pathogenesis of age-related macular degeneration (AMD). The safety and efficacy of avacincaptad pegol (Zimura, IVERIC bio Inc, New York, NY), a C5 inhibitor, were assessed in participants with geographic atrophy (GA) secondary to AMD (GATHER1 Study).
International, prospective, randomized, double-masked, sham-controlled, pivotal phase 2/3 clinical trial.
A total of 286 participants with GA secondary to AMD.
The primary efficacy endpoint was the mean rate of change in GA over 12 months measured by fundus autofluorescence (FAF) at 3 timepoints: baseline, month 6, and month 12.
The reduction in the mean rate of GA growth (square root transformation) over 12 months was 27.4% (P = 0.0072) for the avacincaptad pegol 2 mg cohort and 27.8% (P = 0.0051) for the avacincaptad pegol 4 mg cohort compared with their corresponding sham cohorts. The results for both dose groups were statistically significant. Avacincaptad pegol was generally well tolerated after monthly administration over 12 months. There were no avacincaptad pegol-related adverse events (AEs) or inflammation. Further, there were no ocular serious AEs (SAEs) and no cases of endophthalmitis. The most frequent ocular AEs were related to the injection procedure.
Intravitreal administration of avacincaptad pegol 2 mg and 4 mg led to a significant reduction of GA growth in eyes with AMD over a 12-month period. Because C5 inhibition theoretically preserves C3 activity, it may offer additional safety advantages. A second confirmatory pivotal clinical trial is underway to confirm the efficacy and safety of avacincaptad pegol in slowing the GA growth (GATHER2 Study).
补体途径可能在年龄相关性黄斑变性（AMD）的发病机制中起关键作用。评估 C5 抑制剂 avacincaptad pegol（Zimura，IVERIC bio Inc，纽约，NY）在继发于 AMD 的地图状萎缩（GA）患者中的安全性和疗效（GATHER1 研究）。
国际、前瞻性、随机、双盲、假对照、关键的 2/3 期临床研究。
共 286 名继发于 AMD 的 GA 患者。
主要疗效终点是通过 3 个时间点（基线、第 6 个月和第 12 个月）眼底自发荧光（FAF）测量的 12 个月内 GA 变化的平均率。
avacincaptad pegol 2mg 队列和 avacincaptad pegol 4mg 队列在 12 个月内 GA 生长的平均速度（平方根转换）分别减少 27.4%（P=0.0072）和 27.8%（P=0.0051），与相应的假对照队列相比。两个剂量组的结果均具有统计学意义。avacincaptad pegol 每月给药 12 个月后通常耐受性良好。没有与 avacincaptad pegol 相关的不良事件（AE）或炎症。此外，没有眼部严重不良事件（SAE）和眼内炎病例。最常见的眼部不良事件与注射过程有关。
avacincaptad pegol 2mg 和 4mg 玻璃体腔内给药可显著减少 AMD 患者 12 个月内 GA 的生长。因为 C5 抑制理论上保留了 C3 的活性，所以它可能具有额外的安全性优势。正在进行第二项确证性关键临床试验，以确认 avacincaptad pegol 在减缓 GA 生长（GATHER2 研究）中的疗效和安全性。
