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

• Published in: Ophthalmology science (Online) Vol. 5; no. 4; p. 100759
• Main Authors: Cheung, Chui Ming Gemmy, Jackson, Timothy L., Wykoff, Charles C., Khanani, Arshad M., Leitch, Ian M., Baldwin, Megan E., Slakter, Jason
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.07.2025; Elsevier
• Subjects: Neovascular age-related macular degeneration; Ophthalmology; Polypoidal choroidal vasculopathy; Sozinibercept; VEGF-C/-D; Polypoidal choroidal vasculopathy; PDT; PCV; IVT; PLANET; CNV; ICG; DARC; SD-OCT; TEAE; BCVA; Neovascular age-related macular degeneration; VEGF-C/-D; EVEREST II; nAMD; Sozinibercept; photodynamic therapy; Digital Angiography Reading Center; treatment emergent adverse event; choroidal neovascularization; spectral-domain OCT; indocyanine green; Efficacy and safety of verteportin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy; Efficacy and safety of intravitreal aflibercept for polypoidal choroidal vasculopathy; best-corrected visual acuity; intravitreal
• ISSN: 2666-9145; 2666-9145
• DOI: 10.1016/j.xops.2025.100759

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; 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. 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.