David A. Eichenbaum, MD, FASRS, Management of AMD/DME - Episode 4
A retina specialist discusses impressions and key takeaway points from the case of an 81-year-old male with treatment-experienced neovascular age-related macular degeneration (nAMD).
David A. Eichenbaum, MD, FASRS: My initial impression of this case was, wow, that’s a bad neovascular macular degeneration. We know that patients typically respond and dry up with high frequency, high potency antiangiogenic monotherapy, but all of us have patients in our practice who are like this poor fellow who just don’t have a complete response to inhibiting the old enemy of VEGF-A [vascular endothelial growth factor-A]. Those patients will hopefully be able to benefit from faricimab and other additional targets that we have in the clinical pipeline, but currently in the real world it’s pleasing to be able to offer patients like this who have bad disease that’s poorly controlled an additional option. In this particular case, I was very happy to see the impressive and striking difference in response.
In my practice, the most common barriers to effective treatment of neovascular macular degeneration are really adherence problems. Patients have trouble coming in for high-frequency injections. If we can give patients agents that are more potent and durable, improve them and keep them improved with a longer interval between visits, then that would be a dramatic difference in my practice’s real-world outcomes. Even in a patient like this who may not be the ideal candidates for rapid extension because of his monocular status and his very challenging lesion, I’m happy to be able to at least think about extension after his being treated for 2 years with every 4-week intravitreal antiangiogenic monotherapy. The bispecificity of the faricimab hopefully will give us the tool to improve this burden that our patients are suffering to maintain their outer retinal anatomy stability.
Looking at patients with neovascular macular degeneration, we often think about dosing after we select a first-line agent. We think about monthly or regular dosing, PRN [as needed] dosing, treat-and-extend dosing, and think about some fixed interval other than monthly once a patient does successfully extend out to a certain point of failure. I am an ardent treat and extender in practice. I typically do a short load with my patients of whatever the first-line agent is that I select with the patient. Then we treat the patient for 3 to 4 monthly injections and then begin to extend. Traditionally, I have extended in 2-week increments. In the typical patient—not this patient, perhaps, who’s monocular with an established difficult-to-treat lesion—a typical treatment-naive patient with faricimab given the design of the registration trial allowing for extension every 4 weeks, I may very well extend the patient at longer intervals in an effort to reduce their burden early in their course of treatment. But any way that I dose patients who are treatment-naive, I do lean heavily on a treat-and-extend protocol.
When a patient does exhibit failure with a first-line agent, I’ll often switch the patient to another agent, especially if the patient is on a step therapy program or some program that restricts choice and the patient is required to start with intravitreal bevacizumab off-label. I’ll often switch the patient, if I can’t extend them successfully, to a more potent, perhaps more durable branded intravitreal agent. Once I do that, I attempt extension again. If the patient does have a pattern where even on the most potent, most durable agent available, they have recurrence of fluid, I usually contract the patient to an interval shorter than that and hold the patient on that interval for a good long time.
Sometimes I will consider rechallenging a patient with extension if the patient has a relatively good second eye and they’re frustrated with injections, but we have other options for that now. We often have clinical trials that patients can enroll in where they may be able to receive investigative therapy that could be longer lasting. And we have the availability of the PDS [port delivery system] implant, which may allow patients truly long intervals between intravitreal or refills of the PDS implant. It’s very important to think about patients, think about their needs, think about their limitations, and try to reduce their treatment burden without compromising the visual acuity results that we know patients are capable of with our current armamentarium of agents.
The 2-year efficacy data that we saw in the TENAYA and LUCERNE trials for faricimab and neovascular macular degeneration were extremely encouraging. We saw patients in the second year when they converged to the PTI [personalized treatment interval] arm achieve Q [every] 16 weeks in their second year of treatment in a proportion that we’ve never seen in a treatment-naive wet macular degeneration population studied for that same amount of time. I’m optimistic that I’ll be able to give patients good results with a longer interval between injections, based on what we learned from the TENAYA and LUCERNE year-2 results. We did see a proportion of patients requiring treatment every 8 weeks in TENAYA and LUCERNE. I’m going to watch those patients who require frequent injections, and in the real world with the flexibility in faricimab labeling, I may even treat the patients every 4 weeks, if necessary, to maintain a dry outer retinal and intraretinal anatomy. Regardless, the proportion of patients who did do well with Q 12-week to Q 16-week extension, which was the majority of patients, encourages me that we may be able to extend our wet macular degeneration patients to a longer interval and reduce their burden with faricimab in ways that we have not been able to before.
When I discussed this case at our live roundtable, I was excited to see people’s response to this striking difference with the change from anti-VEGF monotherapy to bispecific angiopoietin-2 suppression and anti-VEGF suppression. This case demonstrates that there is not a one-size-fits-all approach for neovascular macular generation, and that there is not a single cytokine or single protein that we can inhibit and expect the best results in all our patients. The discussion that ensued made me so happy and proud to be a retina specialist, because we’re just at the dawn of the additional target era with the commercial approval of faricimab. I’m optimistic that with the pursuit of science and ongoing clinical investigations, we will have a variety of targets that we can approach. We see this in other therapeutic areas. We see this in cancer, not necessarily looking strictly at biologics or protein inhibition, but looking at optimizing patients’ outcomes by using a combination of approaches and looking at a combination of mechanisms of action. I’m happy we can finally do that in the real world with the commercial approval of faricimab. And at our live roundtable, the audience was equally enthusiastic that we have a new biologic target to pursue.
The take-home from this is that it’s very important to continue to stay on top of new data in our field and continue to have all of the available agents at our disposal. In diabetic macular edema, we have antiangiogenic monotherapy, we have corticosteroid therapy, and now we have bispecific therapy. Of course, in diabetes, we also have laser and surgery. Because there’s so much going on in a diabetic patient you can really tailor your treatment to optimize that patient’s outcome. In macular degeneration, we don’t have quite as big of a quiver as we do in diabetes, but we do have the first bispecific therapeutic looking at a second target. I think it’s going to be fun for each of the retina specialists in the real world to give it a shot and see where it fits into the therapeutic armamentarium.
As of July 2022, there have been 70,000 vials of faricimab delivered, and I’m happy that the ASRS [American Society of Retina Specialists] and the American Academy of Ophthalmology have been watching the safety of this agent, along with the greater retina community. We have not had safety concerns similar to the clinical trials in which there’s been no intraocular inflammatory event associated with retinal vasculitis or occlusive retinitis. I’m happy that we have a new agent, which seems to have a very favorable safety profile that may be able to move the needle for our patients. Thank you for watching this Modern Retinaä presentation. I’ve enjoyed talking about these cases, and I hope everyone found this to be a rich and informative use of their time.
Transcript Edited for Clarity