A conversation on conbercept, the new anti-VEGF in town

Conbercept has been shown in Phase III clinical studies to be safe and effective even with a quarterly dosing regimen and may be beneficial in improving patient compliance.

vision of someone with amd

This is how someone with macular degeneration sees the world. Patients with AMD have poor central vision.

Age-related macular degeneration (AMD) is the most common cause of blindness in individuals >50 years of age, with the worldwide prevalence expected to double in 2020. Agents that inhibit angiogenesis by binding to vascular endothelial growth factor (VEGF) has been the cornerstone of disease management. Examples of anti-VEGF drugs used in intraocular injections are ranibizumab, becizumab, and aflibercept. These drugs require frequent dosing and visits, which are costly and may inhibit compliance.

Conbercept is an anti-VEGF agent developed in China. It is a 141-kDa fusion protein created via the gene recombination of VEGF receptor domains with the Fc fragment of human immunoglobulins. Because of the addition of a binding domain, the receptor-ligand complex is more stable, and the half-life of conbercept has increased.

Previous phase I and II studies have shown that conbercept successfully improved visual acuity and reduced central retinal thickness (CRT) and the area of choroidal neovascularization (CNV). The main purpose of this PHOENIX phase III clinical trial was to determine the efficacy of less frequent dosing intervals in patients with AMD.

This study was a 12-month prospective randomized, double-masked, multi-center, sham-controlled, phase III clinical trial conducted at 9 sites in China. Sham treatments served as control. A total of 124 patients enrolled and were randomized into either the control or treatment group in a 1:2 ratio, with 123 patients completing the study to the primary endpoint at 3 months. The conbercept group was treated with 3 monthly injections (0.5 mg) and then 1 every quarter, while the control group received 3 monthly sham injections, then 3 monthly conbercept injections, and finally quarterly treatments.

Results showed a significant improvement in patients after 3 monthly treatments in 3 months. There were also significant differences in the mean decrease in CRT, leakage area, and CNV area. At the end of 12 months, there was little significant difference between the two groups, likely due to the eventual administration of anti-VEGF treatment. Furthermore, the improvements observed were maintained even with greater intervals in between treatments.

Conbercept was also safely tolerated. The most common eye adverse events were similar to those seen in intravitreal injections, such as conjunctival hemorrhage and increased intraocular pressure.

These findings show that because of its safe and effective quarterly dosing regimen, conbercept may be a more patient-friendly alternative to other VEGF treatments.

Liu, K., Song, Y., Xu, G., Ye, J., Wu, Z., & Liu, X. et al. (2019). Conbercept for Treatment of Neovascular Age-related Macular Degeneration: Results of the Randomized Phase 3 PHOENIX Study. American Journal of Ophthalmology, 197, 156-167. doi: 10.1016/j.ajo.2018.08.026

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