The Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting is one of the major professional meetings in the field of ophthalmology and vision research around the globe. On 7th May, 2025 (MST), RemeGen (688331.SH/09995.HK) announced the results of phase II clinical study on RC28-E, its independently-developed first-in-class VEGF/FGF dual-target fusion protein, in treating diabetic macular edema (DME) through oral presentation at ARVO 2025 in Salt Lake City, Utah. The results showed that RC28-E could improve patients’ best corrected visual acuity (BCVA), reduce central subfield thickness (CST), effectively relieving macular edema.

The phase 2 clinical study reported in this meeting was led by Professor Youxin Chen from Peking Union Medical College Hospital. It was a prospective, randomized, active-controlled, open-label and multi-center phase II clinical study, designed to compare the results between the RC28-E treatment group and the single-target anti-VEGF treatment group, to evaluate the efficacy and safety of RC28-E in treating DME at different doses and in different dosing regimens.

As designed in the protocol, 63.5% of the enrolled participants were treatment-naïve and 36.5% received anti-VEGF treatment in the study eye previously in this study. The BCVA of enrolled participants ranged from 73 to 24 and the CST was 300 µm or higher at baseline. Besides the single-target anti-VEGF treatment group, 4 RC28-E treatment groups were designed by different dose and dosing regimen in this study. The primary endpoints in this study were the change from baseline in BCVA at Week 24 and that at Week 52.

According to the result, RC28-E injection effectively improved the visual acuity of DME patients. At Week 52, the BCVA increased by 8.4 letters, 5.5 letters, 9.5 letters, 9.2 letters and 9.7 letters from baseline in the single-target anti-VEGF treatment group, 1.0 mg Q8W group, 1.0 PRN group, 2.0 mg Q8W group and 2.0 mg Q8W group respectively.

In terms of safety, the result demonstrated that RC28-E was well tolerated in patients. The incidences of ocular adverse events (AEs) and non-ocular AEs were similar to those in the single-target anti-VEGF treatment group.

An article on this study has been published in British Journal of Ophthalmology, a top international journal for ophthalmologists and visual science specialists. According to Professor Chen, the principal investigator, this study was designed to evaluate the efficacy and safety of RC28-E, a fusion protein targeting both VEGF and FGF pathways, among patients with DME, and the results were encouraging: BCVA gains and CST reduction were observed in all RC28-E treatment groups, signaling favorable efficacy in relieving macular edema. This novel investigational agent also demonstrated the potential to better inhibit the VEGF pathway activation and prevent subretinal fibrosis, offering a promising treatment option with improved benefits for DME patients.

DME, characterized by retinal thickening due to capillary leakage in the macula, is a common cause of central vision impairment. It may occur in any stage of diabetic retinopathy (DR). China has the largest population living with diabetes. The research and consulting firm Frost & Sullivan projects that 7.89 million Chinese people will suffer from DME by 2025 and the consequent vision loss will pose a major public health challenge to this country. The current standard of care for DME is anti-VEGF therapy which has been criticized for its burden of frequent monitoring and injection. However a substantial number of patients do not respond or respond poorly to this treatment despite intensive injection, suggesting huge unmet clinical needs.

RC28-E is a first-in-class VEGF/FGF dual-target fusion protein developed by RemeGen for ocular disorders. It inhibits angiogenesis and vasculogenesis by simultaneously binding to members from VEGF and FGF families. Its distinct structure enables superior efficacy in clinical trials while overcoming the limitation of the single-target VEGF inhibitors. The innovative dual-target humanized fusion protein may extend half-life, reduce dosing frequency and improve patient experience.

The follow up of a phase 3 study (NCT05885503, study ID: 28C005 ) on RC28-E among DME patients has been completed and a Biologic License Application (BLA) submission is planned to be filed in the second half of 2025. A phase 3 study (NCT05727397, study ID: 28C004) on RC28-E among patients with age-related macular degeneration is ongoing and BLA for this indication may be submitted in the first half of 2026.

Reference

Zhang W, et al. Simultaneous inhibition of fibroblast growth factor-2 and vascular endothelial growth factor- a with RC28- E in diabetic macular edema: a phase 2 randomised trial. Br J Ophthalmol 2025;0:1–7. doi:10.1136/bjo-2024-326006