Novel Drug Delivery System for the Management of Wet AMD - Episode 9

Innovative Therapies on the Horizon to Treat AMD

June 14, 2021
Carl Regillo, MD, Thomas Jefferson University School of Medicine

,
Diana Do, MD, Stanford University School of Medicine

Carl Regillo, MD and Diana Do, MD react to newer therapies being explored for wet AMD and discuss their place in future therapeutic algorithms.

Carl Regillo, MD: Besides gene therapy, we hopped over some other potentially very useful, valuable, and promising intravitreal biologic injections, going back to anti-VEGF–like approach of injecting in the office. Can you tell me, Diana, a bit about what else is out there on the horizon?

Diana Do, MD:
Sure. There are some exciting new agents also in late stage development. One of them is KSI-301, which is an intravitreal anti-VEGF agent built on a novel ABC platform. ABC stands for antibody biopolymer conjugate, and this medicine is designed for enhanced durability with up to 6 months of VEGF suppression via a single injection. That is also in phase 3 clinical trials right now in wet macular degeneration, diabetic macular edema, and retinal vein occlusion, and the early data have been very promising, with robust visual acuity gains, long duration of VEGF suppression with the need for very few repeat injections, and fortunately no safety signals. I think that’s a very promising program in late stage development. Carl, you’ve had some experience with that. What are your thoughts on KSI-301?

Carl Regillo, MD: I agree. KSI is looking very promising in that category of second-generation anti-VEGF therapy with greater durability. It seems to work as well; it seems to be as safe, although that experience is still quite limited, but nonetheless looking good. Durability, boy that looks to be at least as good as faricimab. We have about 60% of patients going 6 months in the maintenance phase. That’s quite good, after the load. This ABC platform effectively doubles or more the half-life of the drug. It’s a nice way to keep it in the vitreous longer, and that’s looking like its mechanism to get that greater degree of durability. I also put that in the next-generation or second-generation anti-VEGF category.

There is another drug that is interesting. It’s not a VEGF-A blocker, but it blocks VEGF-C and VEGF-D, and is called OPT-302. That’s a fusion protein that blocks C and D. This is an add-on; it’s not a standalone drug. In phase 2 it was added to VEGF-A blocker ranibizumab and did show enhanced vision benefit. It’s aiming at getting maybe better visual acuity outcomes, not necessarily greater durability, because it has to be injected pretty frequently, either every month or every other month, that’s been tested now in phase 3. That’s the only thing on the horizon that might actually get us better acuity. We mentioned limited durability and hoping to get more durable drugs as our big unmet need, and it is. But getting some better vision outcomes of course would be welcome, and that’s working by this combo approach, VEGF-A blockade like we’ve been doing and is still coming, and then adding in a VEGF-C and VEGF-D blocker. Again, an intravitreal injection, fusion protein, and it’s combination therapy, so it’s got to show superiority in vision to what we’re using now.

Then there is this class of tyrosine kinase inhibitor [TKI] molecules, small molecules that have to be packaged in a sustained-release platform, all of which are being injected intravitreally. It’s not a surgery, and there are 4 programs. Three are intravitreal injections, either suspension of microparticles with given TKI, or maybe a biodegradable implant injected intravitreally. There is even a suspension of TKI suprachoroidal injection. They are all aiming to get an anti-VEGF–like effect over about 6 or more months, but that has yet to be demonstrated adequately. What are your thoughts about what you’re hearing about these TKIs?

Diana Do, MD: I think it’s terrific to see all of this innovation continue to push the field forward for patients. It’s wonderful to think out of the box. Certainly, there is room for improvement because not all patients have an optimal response to VEGF inhibitors, and angiogenesis is complicated. There are lots of different cytokines and molecules in play. I think exploring these different inhibitors is a terrific way to try to improve the outcome for all patients. I’ll be excited to see more data as they emerge.

Carl Regillo, MD: In the TKI category, there are few things they have to prove. They have to prove they work as well as our anti-VEGF biologics, have to be as safe, and truly give us the durability factor, give us 6 months or more, not just 3 or 4 months, because the other medicines we’ve been talking about like faricimab and KSI are probably going to achieve that 3 or 4 or more benchmark and durability. They’ve got a hurdle there to try to stack up to what’s on the near horizon with biologics, again KSI-301, faricimab, and then we’ve got the port [Port Delivery System], all in the very near future. A lot is going to be in our hands. There will be a lot of choice for our patients, and that’s all good in terms of decreasing treatment burden with greater durability and hopefully getting better vision outcomes in practice.

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Transcript Edited for Clarity

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