Cheung Chui Ming Gemmy, Jackson Timothy L, Wykoff Charles C, Khanani Arshad M, Leitch Ian M, Baldwin Megan E, Slakter Jason
Medical Retina Department, Singapore National Eye Center, Singapore Eye Research Institute, Singapore, Singapore.
Faculty of Life Sciences and Medicine, Kings College London, London, United Kingdom.
Ophthalmol Sci. 2025 Mar 12;5(4):100759. doi: 10.1016/j.xops.2025.100759. eCollection 2025 Jul-Aug.
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).
Prespecified subgroup analysis of a randomized, double-masked, sham-controlled phase IIb trial.
Adults with treatment-naïve neovascular age-related macular degeneration.
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).
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.
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; = 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.
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.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
本研究旨在评估新型VEGF-C和VEGF-D“陷阱”抑制剂索金单抗与雷珠单抗联合治疗息肉状脉络膜血管病变（PCV）的疗效。
一项随机、双盲、假对照IIb期试验的预设亚组分析。
初治的新生血管性年龄相关性黄斑变性成人患者。
参与者按1:1:1随机分组，每4周接受共6次玻璃体内注射0.5mg雷珠单抗，分别联合0.5mg索金单抗、2mg索金单抗或假注射（对照）。在独立影像中心，由蒙面阅片者根据多模态影像（包括光学相干断层扫描（OCT）（有切迹、尖峰或多叶状色素上皮脱离，内边界有或无高反射环）、眼底照相（视网膜下橙色结节）和荧光素血管造影（典型的主要隐匿性多灶性病变））在基线时确定活动性PCV。
主要终点是至第24周最佳矫正视力（BCVA）相对于基线的平均变化。次要终点包括BCVA相对于基线水平的分类变化、病变形态的解剖学变化和安全性。
366名参与者中，根据预设标准有66名（18%）被确诊为PCV。索金单抗联合治疗产生了剂量反应，从基线至第24周，BCVA平均变化分别为+13.54（2mg组，n = 22）和+10.87（0.5mg组，n = 24）字母，而雷珠单抗组（n = 20）为+6.9字母。2mg索金单抗联合治疗组的BCVA改善优于雷珠单抗组（最小二乘均值相差6.7字母；P = 0.0253），更多参与者视力提高≥10字母（77.3%对47.4%）和≥15字母（分别为40.9%对31.6%），视力下降≥5字母的参与者更少（4.5%对15.8%）。解剖学反应与功能结果一致，在第24周时，2mg索金单抗联合治疗组视网膜下液（19%）或视网膜内囊肿（9.1%）的参与者少于雷珠单抗单药治疗组（分别为42.1%和25%）。索金单抗联合治疗的安全性与雷珠单抗相似。
在PCV患者的这一预设IIb期亚组中，与雷珠单抗单药治疗相比，通过抑制VEGF-C/-D的索金单抗联合治疗在视觉和解剖学结果方面取得了改善，这与总体人群一致。
在本文末尾的脚注和披露中可能会找到专有或商业披露信息。
