Innovent Biologics Inc. released data supporting its second phase 2 study on its neovascular (wet) age-related macular degeneration (nAMD; wet AMD) candidate IBI302 (efdamrofusp alfa).
Let’s start with Innovent.
Founded in 2011, the Suzhou, China-based biopharmaceutical company is focused on the development, manufacturing, and distribution of monoclonal antibody drug candidates in treating oncology, autoimmune, cardiovascular, and ophthalmology.
See here for its current product line pipeline in development (including four in ophthalmology).
Note: Up until this month, the company’s U.S. headquarters and wet lab were located in Rockville, Maryland. Based on reports, however, Innovent has eliminated its entire U.S. research team, with plans to close the facility in the near future.
Yikes! Good to know … now let’s talk about IBI302.
IBI302 is a high-dose, recombinant human vascular endothelial growth factor receptor (VEGFR)-Fc-Human CR1 fusion protein injection.
Its purpose: to improve vasopermeability and reduce leakage by blocking the VEGF-mediated signaling pathway, while also reducing the complement pathway-driven inflammatory response in wet AMD.
How does it do this?
The therapeutic contains two different proteins:
- N-terminus: this site binds to molecules within the VEGF family to block VEGF-controlled signaling and prevent vascular epithelium proliferation and angiogenesis.
- C-terminus: this site binds complement and can inhibit both the classic and alternative complement pathways to reduce the inflammatory response.
Click here to learn about how these proteins work to treat wet AMD.
Now talk about this study.
The multicenter, randomized, double-masked, active-controlled phase 2 clinical study (NCT05403749)—one of two phase 2 studies conducted on wet AMD in a combined total of 360+ participants, according to Innovent—enrolled 132 patients.
- The purpose: to evaluate the longer interval of intravitreal injection of high-dose IBI302 over 52 weeks.
- The setup: Participants were randomized 1:1:1 into three groups:
- IBI302 6.4 mg group
- IBI302 8.0 mg group
- Aflibercept 2.0 mg group
- The dose intervals:
- Following loading therapy, both IBI302 groups were dosed with adjusted intervals every 8 weeks or every 12 weeks, depending on patients’ response to the loading therapy
- Following loading therapy, the aflibercept group was dosed every 8 weeks
And the outcome measures?
Per Clinical Trials, the primary endpoint was the change in best-corrected visual acuity (BCVA) in the study eye, measured from baseline to week 40 (modified from week 52 in the original protocol).
For secondary endpoints, click here.
What were the findings?
Overall, the primary endpoint was successfully met, according to Innovent, with both IBI302 groups showing non-inferior BCVA gains compared to the aflibercept group.
Talk numbers.
At week 40, the mean change (from baseline) in central subfield thickness (CST) was:
- IB302 6.4 mg group
- -163.19 μm
- IBI302 8.0 mg group
- -184.46 μm
- Aflibercept 2.0 mg group
- -108.23 μm
Did any participants extend their dosing intervals?
Yes! An estimated 81% and 88% of patients in the IBI302 6.4 mg and 8.0 mg groups did so, respectively,
This, Innovent reported, was similar to the 83% of subjects dosed every 12 weeks with aflibercept 8.0 mg (Eylea HD, Regeneron) in the PULSAR trial as well as 79.7% and 77.8% of subjects dosed every 12 weeks with faricimab-svoa (Vabysmo, Genentech) in the TENAYA and LUCERNE trials, respectively, by an indirect comparison.
So in a nutshell?
Innovent reported a favorable overall safety profile consistent with previous studies on IBI302.
So what’s next?
According to Dr. Lei Qian, Innovent’s vice president of Clinical Development, the company will continue to investigate the long-interval dosing efficacy and safety of IBI302 as a high dose in the phase 3 STAR trial, which was initiated in October 2023.