Innovent Biologics announces that the first patient has been successfully dosed in a phase 2 clinical trial for IBI302, a first-in-class ophthalmic recombinant human anti-VEGF and anti-complement bi-specific fusion protein.
This study is a randomized, double-blind, multicenter, active-controlled phase 2 study in subjects with active subfoveal or parafoveal choroidal neovascularization secondary to neovascular age-related macular degeneration (nAMD). The primary objective of the study is to evaluate the efficacy and safety of IBI302 in the treatment of nAMD.
As the first bispecific fusion protein targeting VEGF and complement, IBI302 can simultaneously inhibit the proliferation of VEGF-mediated signaling pathway and reduce the inflammatory response mediated by complement activation, according to a company news release. The results of two phase 1 single/multiple-dose escalation studies have preliminarily shown the good safety and efficacy of IBI302 in patients with nAMD with improvement in best-corrected visual acuity, reduction in retinal thickness, and leakage and total area of neovascularization in terms of efficacy. The overall safety profile is similar to that of marketed single-target anti-VEGF drugs. Therefore, in addition to evaluating the efficacy of IBI302 in improving visual acuity and retinal thickness, the effect on macular atrophy and fibrosis will be focused in the ongoing phase 2 study.
Professor Xiaodong Sun from General Hospital affiliated to Shanghai Jiao Tong University, the principal investigator of the study, stated “Currently, intravitreal injection of anti-VEGF drugs have become the first-line treatment for neovascular fundus diseases, but globally there’s still no bispecific fusion protein in clinical studies targeting both VEGF and complement. As a global innovative drug for the treatment of ocular fundus diseases, the results of IBI302 in single-dosed and multiple-dosed studies suggest the good safety and clear efficacy in improving visual acuity and retinal thickness. The phase 2 clinical study will explore the efficacy of this drug for macular atrophy and retinal fibrosis, which we hope could overcome the limitations of current therapies and benefit more patients.”
“IBI302 is independently developed by Innovent as an first-in-class anti-VEGF and anti-complement bispecific drug that blocks VEGF while suppressing the activation of the complement system, and has been supported by the Major New Drug Project of the Ministry of Science and Technology as a Class 1 new drug. IBI302 was designed to provide more targeted treatment and interventions to the cause of nAMD by adding additional targets. We hope that we can provide physicians with a better treatment option and benefit more patients with fundus diseases and their families through the clinical development of IBI302 as an innovative target.” said Dr. Lei Qian, Executive Director of Department for Medical Science and Strategies of Special Disease of Innovent.
IBI302 is an innovative bispecific anti-VEGF and anti-complement recombinant fully human fusion protein, which can inhibit VEGF-mediated neovascularization and complement activation pathways simultaneously. The N-terminus is a VEGF domain that can bind to the VEGF family, block VEGF-mediated signaling pathway, inhibit vascular epithelium proliferation and angiogenesis, and improve vasopermeability and reduce leakage. The C-terminus of IBI302 is the complement binding domain that can inhibit the activation of the classic pathway and alternative pathway of complement through the specific binding of C3b and C4b, and reduce the inflammatory response mediated by the complement.
The results of the phase 1 single-dose escalation clinical trial for IBI302 were released at 2020 American Academy of Ophthalmology in November 2020. A total of 31 subjects were enrolled in the completed phase 1 study. All subjects received a single intravitreal injection of IBI302. No serious adverse event or dose limiting toxicity was reported. The study demonstrated good safety and tolerability of IBI302. One week after administration, improved vision and reduction of retinal edema were observed. By 28 days after administration, all 31 subjects’ best corrected visual acuity increased by 6 letters on average compared to baseline, the average central retinal thickness decreased by 141.2 microns compared to baseline, and the efficacy of some patients lasted until 6 weeks after administration.