Carl D. Regillo, MD, FACS; Blake Anthony Cooper, MD, MPH; Michael A. Klufas, MD; and David R. Lally, MD, talk about important data that has awaited for several newer and investigational therapies for DME and AMD.
Carl D. Regillo, MD, FACS: Blake, are you aware of any ongoing or expected data coming out within the next year or so with faricimab, with the port-delivery system for either disease state?
Blake Anthony Cooper, MD, MPH: As you mentioned, Carl, our patients are living longer with their disease, so it’s important for us to continue to follow patients who were enrolled in clinical trials to see how their long-term visual outcomes are doing. Fortunately, for both faricimab and the port-delivery device, those enrolled in initial trials for FDA approval were able to continue in long-term safety and efficacy trials for both patients with diabetic macular edema [DME] as well as diabetic macular degeneration. Results will probably not be readily available for at least 1 to 2 years for the TENAYA and LUCERNE trials, which were the efficacy of faricimab in macular degeneration. The trials for YOSEMITE and RHINE will hopefully be within the next year or 2.
Carl D. Regillo, MD, FACS: We’re going to see extension data and some nice long-term data long beyond 2 years for these therapeutics, for these disease states, which is unique. With the previously studied drugs, we didn’t have clinical trial data beyond 2 years, or 3 for DME. We’re also going to have some global data from the port-delivery system with some tweaks in the way it’s refilled, comparing 24- to 36-week refill regimen; that’s going to be interesting. Everyone wants to know the long-term safety of the port-delivery system, and that extension trial is going to be particularly valuable.
Dave, what metrics or clinical diagnostics would you like to see included in some of these long-term extension trials of faricimab, port-delivery system, and so forth?
David R. Lally, MD: We want to continue to follow both the safety and efficacy of the treatments. If we’re talking about the efficacy, we want to the see the best corrected visual acuity over the long term. Vision is quite important for patients. Patient-reported outcome measures over the long term are important as well. They’re also important for payers. How did these treatments do for the patient from the patient perspective over the long term? Looking at the anatomy, the OCT [optical coherence tomography], and looking at the fluid and the control of exudation in both of these diseases over the long term is going to be important. Because as previously mentioned, these diseases often require years of therapy, much longer than a 1- to 2-year clinical trial.
Some other things that would be interesting to see in patients with diabetic retinopathy and diabetic macular edema, specifically with port delivery, would be looking at correlating the hemoglobin A1C [glycated hemoglobin] to the control of the fluid over the long term. Monitoring hemoglobin A1C will be interesting to see whether that plays a role. For diabetic retinopathy, looking at peripheral nonperfusion and macular ischemia. We haven’t seen dramatic improvements in nonperfusion with our standard intravitreal anti-VEGF therapies, but maybe it will be different in the port-delivery system.
Another thing that would be interesting in diabetic retinopathy and edema would be looking at another functional measure, like microperimetry. I’m not sure if they’re following that in the trials, but there’s only a moderate correlation between fluid and visual acuity. That might be another functional test that gives us some more long-term understanding of how these therapies are doing from a functional standpoint for our patients.
Carl D. Regillo, MD, FACS: I’m going to also throw in analysis on geographic atrophy over the long run with the port-delivery system. There’s some suggestion that more frequent injections yield higher rates of atrophy in our patients with wet AMD [age-related macular degeneration]. We don’t think that’s a drug adverse effect. It may be the natural course of AMD, but we don’t know for sure. A̶behaves with true, sustained delivery more on the order of 0—order kinetics if you will, although not quite. It might give us something different, maybe something safer, maybe something not. Some additional analysis there would be useful.
Blake Anthony Cooper, MD, MPH: I’m also excited to see that there’s a clinical trial that’s incorporating use of continuous glucose monitors. Hopefully those data will give us a better understanding of disease progression for diabetic retinopathy. As we have more patients coming in with continuous glucose monitors, it’s important to watch their coefficient variance for glucose. It’s a pretty easy metric to get from their downloads that looks at the variability of glucose throughout the day. As we know, A1C is the average glucose level over a 3-months period, but it’s that time in range and the variability within that range that most likely could be worsening disease. We need to make sure their coefficient variance of glucose is below 36%. That’s an important variable.
Transcript Edited for Clarity