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Sozinibercept (Anti-VEGF-C/-D) Combined with Ranibizumab for Polypoidal Choroidal Vasculopathy: Phase IIb Predefined
Chui Ming Gemmy Cheung1, Timothy L Jackson2, Charles C Wykoff3,4
1Medical Retina Department, Singapore National Eye Center, Singapore Eye Research Institute, Singapore, Singapore.
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 Disclosures:
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Insights
Sozinibercept combined with ranibizumab improved vision and reduced lesion activity in polypoidal choroidal vasculopathy (PCV) patients. This combination therapy demonstrated superior visual gains and anatomical improvements compared to ranibizumab alone.
Area of Science:
- Ophthalmology
- Medical Research
- Pharmacology
Background:
- Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular age-related macular degeneration.
- Current treatments like ranibizumab target VEGF-A, but PCV involves VEGF-C and VEGF-D pathways.
- Sozinibercept is a novel inhibitor targeting VEGF-C and VEGF-D.
Purpose of the Study:
- To evaluate the efficacy of sozinibercept in combination with ranibizumab for PCV treatment.
- To assess the impact of VEGF-C and VEGF-D inhibition on visual acuity and anatomical outcomes in PCV.
Main Methods:
- A randomized, double-masked, sham-controlled phase IIb trial subgroup analysis.
- 66 participants with treatment-naïve PCV received 6 intravitreal injections of ranibizumab 0.5 mg with either 0.5 mg or 2 mg sozinibercept, or sham.
- Primary endpoint: change in best-corrected visual acuity (BCVA) at week 24; secondary endpoints: anatomical changes and safety.
Main Results:
- The 2 mg sozinibercept combination group showed a significantly greater mean BCVA gain (+13.54 letters) compared to ranibizumab alone (+6.9 letters) at week 24 (P=0.0253).
- More participants in the 2 mg sozinibercept group achieved ≥10 letter gains (77.3%) and ≥15 letter gains (40.9%) versus the ranibizumab group (47.4% and 31.6%).
- Anatomical improvements were observed, with fewer participants in the 2 mg sozinibercept group experiencing subretinal fluid (19%) or intraretinal cysts (9.1%) compared to ranibizumab monotherapy (42.1% and 25%).
Conclusions:
- Sozinibercept combination therapy, by inhibiting VEGF-C/-D, significantly improved visual and anatomical outcomes in PCV patients.
- The 2 mg dose demonstrated a dose-dependent response, offering superior efficacy compared to ranibizumab monotherapy.
- The safety profile of sozinibercept combination therapy was comparable to ranibizumab monotherapy.
