ASRS 2024: Durability of combination therapy of sozinibercept in nAMD and DME

Nathan Steinle, MD, spoke with Modern Retina about the ongoing research on the durability of sozinibercept in combination therapy with anti-VEGF-A treatments at the annual ASRS meeting in Stockholm, Sweden.

Video Transcript:

Editor's note: The below transcript has been lightly edited for clarity.

Nathan Steinle, MD:

Hi, my name is Nathan Steinle, and I'm with California Retina Consultants, with Retina Consultants in America in Santa Barbara, California. I'm really excited to be here in Stockholm, Sweden for the first time for the ASRS annual meeting. And what I gave a talk about here was combination therapy for both neovascular AMD and DME. And the combination therapy is a molecule called sozinibercept in combination with either aflibercept or ranibizumab, again for DME or for neovascular AMD.

So, what is sozinibercept? Why are we talking about this? Well, it's a C and D inhibitor, not a VEGF-A inhibitor, but C and D inhibitor. And by inhibiting C and D, you stop the activation of VEGF-2 and-3. And we think that that is important because in patients who get VEGF-A suppression, they have upregulation of C and D, and it might be some of the reasons why some of our patients are suboptimal responders to our current VEGF-A inhibition therapies.

So, what did I show here? I showed the Phase 1 and Phase 2 trial results, both for DME and for AMD, and specifically looking at superior visual acuity result. And our Phase 2 trials for neovascular AMD had over 360 patients looking at either monotherapy with ranibizumab or combination therapy of ranibizumab plus sozinibercept. And the combination therapy had up to about a 6-letter difference in improvement versus those patients who received monotherapy with ranibizumab at the 6-month mark.

Well, where do we go from here? Okay, so we've got this combination therapy, we put sozinibercept, can you put it with both aflibercept or ranibizumab? Well, we think so. If you look at the Phase 1 data, we looked at both aflibercept and ranibizumab being combined with sozinibercept, so I think it's hopefully going to be VEGF-A agnostic, meaning it'll probably work with any anti-VEGF-A. Specifically, so far we've looked at aflibercept and ranibizumab. Well, going forward now we have 2 very large global trials, the SHORE trial and the COAST trial. Each of them are 1,000 patients looking at neovascular AMD. The COAST trial looked at combination sozinibercept and aflibercept, and the SHORE trial looked at combination sozinibercept and ranibizumab. Two different doses of sozinibercept: you have 4- or 8-week dosing in combination with on-label therapy for aflibercept in COAST or ranibizumab in SHORE. What we're looking at is the 1-year primary endpoint, which will come out early- to mid-2025. So exciting things. Both these 1,000 patient trials, which are huge trials, are fully enrolled and ongoing now. We'll know the results again early- to mid-2025. So, stay tuned for more for combination therapy with sozinibercept.