Sozinibercept (Anti-VEGF-C/-D) Combined with Ranibizumab for Polypoidal Choroidal Vasculopathy: Phase IIb Predefined Subgroup Analysis

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-03-12 DOI:10.1016/j.xops.2025.100759

Chui Ming Gemmy Cheung MD, FRCOphth , Timothy L. Jackson PhD, FRCOphth , Charles C. Wykoff MD, PhD , Arshad M. Khanani MD, FASRS , Ian M. Leitch PhD , Megan E. Baldwin PhD , Jason Slakter MD

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Abstract

Purpose

The aim of this study was to assess the efficacy of sozinibercept, a novel “trap” inhibitor of VEGF-C and VEGF-D, when combined with ranibizumab for the treatment of polypoidal choroidal vasculopathy (PCV).

Design

Prespecified subgroup analysis of a randomized, double-masked, sham-controlled phase IIb trial.

Participants

Adults with treatment-naïve neovascular age-related macular degeneration.

Methods

Participants were randomized 1:1:1 to receive a total of 6 intravitreal injections of ranibizumab 0.5 mg given 4-weekly, in combination with either 0.5 mg sozinibercept, 2 mg sozinibercept, or sham injection (control). Active PCV was determined at baseline by masked readers at an independent imaging center based on multimodal imaging, including OCT (notched, sharply peaked, or multilobular pigment epithelial detachments with or without a ring of hyperreflectivity along the inner border), fundus photography (subretinal orange nodules), and fluorescein angiography (typical primarily occult multifocal lesions).

Main Outcome Measures

The primary end point was mean change from baseline in best-corrected visual acuity (BCVA) through week 24. Secondary end points included categorical changes in BCVA from baseline, anatomical changes in lesion morphology, and safety.

Results

Of 366 participants, PCV was identified in 66 (18%) using predefined criteria. Sozinibercept combination therapy produced a dose response, with a mean BCVA change from baseline to week 24 of +13.54 (2 mg, n = 22) and +10.87 (0.5 mg, n = 24) letters compared with +6.9 letters for ranibizumab (n = 20), respectively. The 2 mg sozinibercept combination group had a superior BCVA gain versus ranibizumab (+6.7 letter difference in least squares mean; P = 0.0253) with more participants gaining ≥10 letters (77.3 vs. 47.4%) and ≥15 letters (40.9 vs. 31.6%) and fewer losing ≥5 letters (4.5 vs. 15.8%). Anatomic responses were consistent with functional outcomes and at week 24, fewer participants in the 2 mg sozinibercept combination group had subretinal fluid (19%) or intraretinal cysts (9.1%) than with ranibizumab monotherapy (42.1% and 25%, respectively). The safety profile of sozinibercept combination therapy was similar to ranibizumab.

Conclusions

In this predefined phase IIb subgroup of patients with PCV, sozinibercept combination therapy through inhibition of VEGF-C/-D achieved improved visual and anatomic outcomes compared with ranibizumab monotherapy consistent with the overall population.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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Sozinibercept（抗血管内皮生长因子-C/-D）联合雷珠单抗治疗多形性脉络膜血管病：IIb期预定义亚组分析

目的本研究旨在评估新型VEGF-C和VEGF-D "陷阱 "抑制剂sozinibercept与雷尼珠单抗联合治疗多形性脉络膜血管病（PCV）的疗效。方法以1:1:1的比例随机分组，每4周接受6次雷尼珠单抗0.5毫克的玻璃体内注射，同时联合使用0.5毫克索西尼贝特、2毫克索西尼贝特或假注射（对照组）。活动性PCV在基线时由独立成像中心的蒙面读片员根据多模态成像确定，包括OCT（缺口、尖峰或多叶状色素上皮脱落，沿内缘有或无高反射环）、眼底照相（视网膜下橙色结节）和荧光素血管造影（典型的主要是隐匿性多灶病变）。主要结果测量主要终点是最佳矫正视力（BCVA）从基线到第24周的平均变化。次要终点包括最佳矫正视力（BCVA）与基线相比的分类变化、病变形态的解剖学变化以及安全性。结果在366名参与者中，有66人（18%）通过预定义标准发现了PCV。Sozinibercept联合疗法产生了剂量反应，从基线到第24周的平均BCVA变化分别为+13.54（2毫克，n = 22）和+10.87（0.5毫克，n = 24）个字母，而雷尼珠单抗（n = 20）为+6.9个字母。与雷尼珠单抗相比，2 毫克索西尼贝特联合用药组的 BCVA 增益更高（最小二乘法均值差+6.7 个字母；P = 0.0253），其中增益≥10 个字母（77.3% 对 47.4%）和≥15 个字母（40.9% 对 31.6%）的参与者更多，而损失≥5 个字母（4.5% 对 15.8%）的参与者更少。解剖反应与功能结果一致，第24周时，2毫克sozinibercept联合治疗组出现视网膜下积液（19%）或视网膜内囊肿（9.1%）的人数少于雷尼珠单抗单药治疗组（分别为42.1%和25%）。结论在这一预定义的IIb期PCV患者亚组中，通过抑制VEGF-C/-D，sozinibercept联合疗法与雷尼珠单抗单药相比改善了视觉和解剖结果，与总体人群一致。

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