RWC 2024: Rationale for the design of the phase 3 superiority clinical trials of sozinibercept combination therapy

David Eichenbaum, MD, spoke with Modern Retina about his presentation at the 2024 Retina World Congress meeting held in Fort Lauderdale, Florida. The presentation was titled, "Rationale for the Design of the Phase 3 Superiority Clinical Trials of Sozinibercept Combination Therapy Targeting Inhibition of VEGF-C/-D and VEGF-A for Neovascular Age-Related Macular Degeneration."

Video Transcript:

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

David Eichenbaum, MD:

Hi I'm David Eichenbaum, director of research at Retina Vitreous Associates of Florida, and I'm very excited to present the rationale for the design of the sozinibercept anti-VEGF-C, and anti-VEGF-D combination treatment with anti-VEGF-A for wet macular degeneration. So we know that in our current wet macular degeneration patients, we couldn't do better with vision when VEGF-A is suppressed by our commercially available agents as a compensatory increase in VEGF-C and -D. And we believe that inhibition with sozinibercept, inhibiting VEGF-C and-D will further reduce the drive of the VEGF receptors and possibly improve the visual outcome in patients with wet macular degeneration. I'm excited about this program, because it's the only program that could disrupt the space with an improvement in visual acuity. Why do we think this drug has that potential? Well, we know from phase 1 and phase 2B designs that sozinibercept is both well-tolerated and seems to show increased efficacy with regards to mean change visual acuity in wet macular degeneration, and the phase 2B, 366 patient clinical trial looking at wet macular degeneration sozinibercept 2 mg in combination with ranibizumab increased visual acuity by over 3 letters and all comers and by over 5 letters and pre-specified high responders with minimally occult and classic lesions in the absence of retinal angiomas proliferation. The phase 3 studies COAST, combining sozinibercept with aflibercept, and is SHORE, combining sozinibercept with ranibizumab, are designed similarly to the phase 2 study, which showed this increased efficacy eliminating patients with a rap and there's a pre-specified hierarchical analysis looking first at patients who are optimal responders minimally classic and occult patients who make up the majority of our real-world with AMD patients. 990 patients per study, and we're putting this to the test. We want to see if we can duplicate this increase in mean change in visual acuity in patients with wet macular degeneration. If we can, we will have the first and only drug program in late phase development, looking not just at increased durability, but increased efficacy in wet macular degeneration, and that is what's exciting about the design of the sozinibercept trials. So a question that we have is if sozinibercept meets its primary endpoint and is approved and shows a meaningful change in best corrected visual acuity superior to anti-VEGF-A monotherapy, where's the wet macular degeneration treatment paradigm going? Well, I certainly believe that this drug would be employed in patients similar to those that come into the clinical trial, because we always want our patients to have their best visual acuity. And we would look to patients with newly diagnosed disease and certainly consider this drug. Of course, we wonder would it also work in patients with treatment experience with wet AMD? Would it work in patients who have visual acuity different than that included in the clinical trial? Would it be broader? Could its use be broader? And those are questions that we're going to have to answer in the real world. If the drug does meet its primary endpoint, I think it would certainly be part of the treatment paradigm for patients with newly diagnosed wet macular degeneration with some visual acuity loss.