目的:评价血管生成素-2(Ang-2)和血管内皮生长因子(VEGF)-A抑制剂法利玛与阿柏西普治疗静脉阻塞患者的24周疗效和安全性。
方法:第三阶段,全球,随机化,双面蒙面,主动对照试验:BALATON/COMINO(ClincalTrials.gov标识符:NCT04740905/NCT04740931;站点:149/192)。
方法:治疗初期中央凹中心累及的黄斑水肿由分支(BALATON)或中央或半视网膜(COMINO)RVO引起的患者。
方法:患者以1:1的比例随机分配至法利单抗6.0mg或阿柏西普2.0mg,每4周一次,共24周。
方法:主要终点:最佳矫正视力(BCVA)从基线到第24周的变化。疗效分析包括意向治疗人群中的患者。安全性分析包括接受≥1剂量研究药物的患者。
结果:注册:BALATON,n=553;COMINO,n=729。从基线到第24周,法利单抗的BCVA增益与BALATON中的阿柏西普相比不差(调整后的平均变化,+16.9个字母[95.03%置信区间(CI),15.7-18.1字母]vs.+17.5字母[95.03%CI,16.3-18.6字母])和COMINO(+16.9字母[95.03%CI,15.4-18.3字母]与+17.3个字母[95.03%CI,15.9-18.8个字母])。在BALATON的第24周时,faricimab和aflibercept相对于基线的调整平均中心子场厚度减少具有可比性(-311.4μm[95.03%CI,-316.4至-306.4μm]和-304.4μm[95.03%CI,-309.4μm])和COMINO(-461.6μm[95.3%CI,-471.3%至-在BALATON的第24周,法利单抗与阿柏西普组的患者比例更高(33.6%vs.21.0%;标称P=0.0023)和COMINO(44.4%与30.0%;标称P=0.0002)。Faricimab耐受性良好,具有与阿柏西普相当的可接受的安全性。在BALATON和COMINO中,接受法利单抗治疗的患者的眼部不良事件发生率相似(16.3%[n=45]和23.0%[n=84],分别)和阿柏西普(20.4%[n=56]和27.7%[n=100],分别)。
结论:这些发现证明了法利单抗的有效性和安全性,Ang-2/VEGF-A双重抑制剂,视网膜静脉阻塞继发黄斑水肿患者。
背景:专有或商业披露可以在本文末尾的脚注和披露中找到。
OBJECTIVE: To evaluate the 24-week efficacy and safety of the dual angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF)-A inhibitor faricimab versus aflibercept in patients with vein occlusion.
METHODS: Phase 3, global, randomized, double-masked, active comparator-controlled trials: BALATON/COMINO (ClincalTrials.gov identifiers: NCT04740905/NCT04740931; sites: 149/192).
METHODS: Patients with treatment-naïve foveal center-involved macular edema resulting from branch (BALATON) or central or hemiretinal (COMINO) RVO.
METHODS: Patients were randomized 1:1 to faricimab 6.0 mg or aflibercept 2.0 mg every 4 weeks for 24 weeks.
METHODS: Primary end point: change in best-corrected visual acuity (BCVA) from baseline to week 24. Efficacy analyses included patients in the intention-to-treat population. Safety analyses included patients who received ≥ 1 doses of study drug.
RESULTS: Enrollment: BALATON, n = 553; COMINO, n = 729. The BCVA gains from the baseline to week 24 with faricimab were noninferior versus aflibercept in BALATON (adjusted mean change, +16.9 letters [95.03% confidence interval (CI), 15.7-18.1 letters] vs. +17.5 letters [95.03% CI, 16.3-18.6 letters]) and COMINO (+16.9 letters [95.03% CI, 15.4-18.3 letters] vs. +17.3 letters [95.03% CI, 15.9-18.8 letters]). Adjusted mean central subfield thickness reductions from the baseline were comparable for faricimab and aflibercept at week 24 in BALATON (-311.4 μm [95.03% CI, -316.4 to -306.4 μm] and -304.4 μm [95.03% CI, -309.3 to -299.4 μm]) and COMINO (-461.6 μm [95.03% CI, -471.4 to -451.9 μm] and -448.8 μm [95.03% CI, -458.6 to -439.0 μm]). A greater proportion of patients in the faricimab versus aflibercept arm achieved absence of fluorescein angiography-based macular leakage at week 24 in BALATON (33.6% vs. 21.0%; nominal P = 0.0023) and COMINO (44.4% vs. 30.0%; nominal P = 0.0002). Faricimab was well tolerated, with an acceptable safety profile comparable with aflibercept. The incidence of ocular adverse events was similar between patients receiving faricimab (16.3% [n = 45] and 23.0% [n = 84] in BALATON and COMINO, respectively) and aflibercept (20.4% [n = 56] and 27.7% [n = 100], respectively).
CONCLUSIONS: These findings demonstrate the efficacy and safety of faricimab, a dual Ang-2/VEGF-A inhibitor, in patients with macular edema secondary to retinal vein occlusion.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.