Retina Society 2024: A comparison of tyrosine kinase inhibitors in development

Sumit Sharma, MD, sat down with Sydney Crago of Modern Retina to discuss his presentation on the 3 tyrosine kinase inhibitors currently in development for the treatment of retina conditions at the Retina Society meeting being held this year in Lisbon, Portugal.

Video Transcript:

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

Sydney M. Crago: Hi, I'm Sydney Crago with Modern Retina and Ophthalmology Times, and I'm here today with Dr Sharma to talk about his presentation at last week's Retina Society meeting. Dr Sharma, can you tell us about your presentation?

Sumit Sharma, MD: Yes, thanks for having me. So I presented on a comparison of the different tyrosine kinase inhibitors that are being developed for intravitreal delivery. And I also gave an update on some of the findings from the DAVIO-2 study for wet age related macular degeneration. And so as we know, we've traditionally used the VEGF inhibitors like a aflibercept, faricimab, bevacizumab, and ranibizumab, which block the receptor on the extracellular side. The tyrosine kinase inhibitors are new mechanisms of action that block, not just one VEGF receptor, but they give us pan-VEGF blockade by blocking the receptor on the intracellular side, and then they also block another category of receptors, including the FGF receptors and the PDG receptors. And so what I presented was an overall overview of the 3 different TKIs being developed for ophthalmic use, including vorolanib, sunitinib, and axitinib, and showed that overall, all 3 of them do a very good job at their clinically given dose, at blocking all the activity. I also talked about the concept of IC-50, and that when you exceed the IC-50, going any higher than that in terms of concentration doesn't give you more efficacy. When you're under the IC-50, it does, there is a difference, but all 3 of the TKIs at their clinical doses that are injected in the eye are very effective and above their IC-50. So there shouldn't be any effect of going higher than that. And the data that I showed basically corroborated those findings. And then I switched gears and showed some of the data on the EYP-1901 specifically, which is vorolanib being developed for wet age-related macular degeneration. And this was studied in both animal models, and now in the DAVIO-2 study, which is a phase 2 study in humans. In the animal models, they very clearly showed that the vvorolanib, when given as a single intravitreal injection, stays above the IC-50 through 9 months in both the retina, vitreous, and the choroid. And then in DAVIO-2, which is a wet age-related macular degeneration study in patients who were previously treated. This is a very treated population. They then got 3 injections, every single patient got 3 injections of aflibercept at baseline, month 1 and month 2, and then were randomized to get 1 of 2 doses of the EYP-1901, or continue on on-label aflibercept Q8 weeks. And what we found was that overall, both visual acuity and CST remained stable out through a year after a single EYP-1901 injection. It was very well-tolerated with a good safety profile. There were no EYP-1901 related ocular or systemic SAEs, and no one discontinued treatment because of the EYP-1901. And most interestingly, out at a year, 50% of patients after a single injection of either of the 2 doses of EYP-1901 remained without needing any supplemental treatment. Interestingly, in the aflibercept Q8 week groups, 68%, so 50 versus 68%, remained supplement-treatment free. And so overall, EYP-1901 was very well-tolerated. It maintained stable visual acuity with strong anatomic control for over 12 months after a single injection. And the phase 3 program for developing EYP-1901 is ongoing.

Sydney M. Crago: How would this benefit patients from, like, a treatment burden standpoint, and physicians from a treatment burden standpoint?

Sumit Sharma, MD: I think it could have a very significant reduction in treatment burden. I mean, if we're seeing, like I said in DAVIO-2, we saw at year, 50% were treatment-free. But at 6 months, it was 62 and 63% that were treatment free. So 2 out of 3 patients could get a single injection once you dry them out, if we follow a similar protocol, right? Three EYLEA injections, and then dry, and then you give them the EYP-1901, and if 2 out of 3 don't need another treatment out through 6 months, that's pretty significant, and I think it significantly reduces the treatment burden in a lot of patients. Now, the phase 2 study wasn't designed to specifically look at every patient and treatment-naive patients. This was a previously-treated, potentially difficult to treat population, and we still got out that far. So in reality, if we look at a treatment-naive population, it may be even a greater proportion than that.