VEGF Inhibitors With Potential to Treat AMD: KSI-301

Karl Csaky, MD, PhD: Lloyd, you’re an academic retina person, but put on your private practice hat. We’re hearing about the tremendous durability of the PDS [port delivery system], but we have other agents that are moving along the pipeline. We have the Kodiak [Sciences] outcomes. Where do you think that bar is in your mind, or in the mind of folks? Is it 16 weeks? Is it from an injection? Carl talked about the cumulative rates. But if you’re down to 3 or 4 injections a year, the cumulative rates start to fall. Walk us through your thinking or what you think your peers are thinking about in terms of this durability issue—the challenges we face, but also what’s coming down the future in terms of faricimab, Kodiak, or other things. Is there some magic number that you’ve been thinking about that we need to get to with an injection?

Lloyd Clark, MD: That’s a fascinating question. We’ve got different strategies going concurrently at the same time, so it’s an exciting time in drug development. We’ve got drugs—for instance, KSI-301, the Kodiak drug—has treatment intervals in their trials as long as 6 months. The idea is that we have a drug in late-phase clinical development that may have similar efficacy to monthly therapy used twice a year. That’s very meaningful, and that impacts the idea of a transformative technology, such as PDS or the holy grail of treatment durability, which is gene therapy.

In the short run, every-4-week management of aggressive disease, the thing that’s exciting about faricimab—when we think about treatment durability—is the ability to use a drug as infrequently as 3 or 4 times a year and manage our most difficult patients. That’s attractive and potentially a paradigm shift in terms of injectable drugs. On the other end of the scale, the PDS is a device for our patients who aren’t difficult to manage. I’m thinking about PDS as a device—at least initially as an AMD [age-related macular degeneration] device—that’s a great choice for patients who are well maintained on regular injections for a long period of time.

The answer is it’s going to be a nuanced question. These disease states are highly heterogeneous. You can’t put patients into large categories. We’re going to figure out how each of these treatment modalities works in terms of maintaining outstanding outcomes and maximizing or reducing treatment interval. It’s going to depend on patient-specific factors as well as disease-specific factors. We may use some of these agents more predominantly in AMD. I think about PDS as a great AMD device, particularly in patients who we can manage every 6 to 10 weeks for injections. Alternatively, faricimab seems like a great drug for diabetes, to be able to manage severe patients less frequently. It’s an exciting time. We’re going to have a lot of choices on the horizon. We’re going to have to get smarter about how we use them and figure out other factors that can help us make good choices.

This transcript has been edited for clarity.