David A. Eichenbaum, MD, FASRS, Management of AMD/DME - Episode 2

Impressions and Takeaway Points From DME Patient Case #1

A retina specialist discusses impressions and key takeaway points from the case of a 74-year-old man with diabetic macular edema (DME).

David A. Eichenbaum, MD, FASRS: My initial impression of this case is that this is a patient with chronic diabetic macular edema who has achieved partial control. It’s the type of patient that we’ve historically said we’re good enough with. We’ve often tried them on corticosteroids like I did with this patient. But if the patient can’t tolerate corticosteroids because of IOP [intraocular pressure] response or other issues, we then revert back to frequent antiangiogenic monotherapy. It’s nice to be able to offer the patients something more. The challenge in this situation is that we do not have a good handle on this type of patient from the registration data for faricimab. Those patients were either treatment-naive or well washed out from diabetic treatment. This patient never would have come into the faricimab registration trial. So we’re working in uncharted territory. However, we do have faricimab as an on-label, commercially available option for these patients. As this case demonstrates, we’ll perhaps have some success in these patients who have been hard to treat with frequent antiangiogenic injections.

To determine the goals of therapy, I really look at the anatomy. This patient had diabetic macular edema with intraretinal fluid at the center of the macula, with decreased visual acuity despite frequent antiangiogenic therapy. My goal is to dehydrate the macula. I often tell patients that I can’t control their vision, but I can work hard to improve their anatomy. So my goal in this specific clinical scenario, in this specific case, is that I want the anatomy to be better. When we achieve that, fortunately in this case, we also achieve an improvement in its subjective and objective acuity.

The role of approved anti-VEGFs [vascular endothelial growth factors] in the treatment of diabetic macular edema has been well established. We’ve used antiangiogenic therapy as our gold standard first-line treatment for the last 10 to 15 years in diabetic macular edema. What we’re seeing now with the faricimab data is the addition of a second target. Bispecific inhibition may be moving us beyond the antigen monotherapy era with regards to durability and efficacy to give our patients overall similar visual acuity outcomes, but with less frequent intravitreal injections. Potency and durability are very important to me when selecting a therapy. That’s why I’ve always looked toward the most potent and most durable agent as a first-line treatment for my diabetic macular edema patients. And we see with the registration data, at least in the clinical trial population with faricimab, that we may be moving into a new era of potency with regards to anatomic improvements and a new era of durability with regards to extended intervals between treatment administrations.

Faricimab is different from other intravitreal agents because it is a bispecific inhibitor. It’s the first bispecific inhibitor for intraocular use. We have suppressed vascular endothelial growth factor A very effectively with off-label and high affinity on-label therapies for 10 to 15 years. What’s remarkable about adding faricimab to the armamentarium is it allows us to inhibit a second cytokine, angiopoietin-2, which has robust basic science evidence as being a mediator of vascular destabilization and leakage through damaged vessels. The addition of inhibition of angiopoietin-2 may help us move beyond the antiangiogenic monotherapy era to give our patients better efficacy and a lower burden of treatment.

The durability of faricimab in the YOSEMITE and RHINE trials is remarkable because we have not seen a population in a randomized controlled prospective trial achieve parity with high-frequency antiangiogenic, anti-VEGF monotherapy with the extended intervals that the faricimab patients in the personalized treatment interval arm enjoyed starting in the first year of treatment, which then continued to have further extension in the second year of treatment. The remarkable thing about giving patients the option of a drug that can extend most of them to Q [every] 12 or 6 week intervals in the first and second year of treatment is that we may be able to see diabetics actually adhere to our recommended intervals for treatment, as opposed to diabetics who do poorly because they cannot adhere to high-frequency injection intervals. I’m hopeful that the addition of this new molecule with its extended durability will allow our patients in the real world to do as well or close to as well as patients in our clinical trials.

What stood out to me after I discussed this case with colleagues at our round table is how enthusiastic retina specialists remain to try something new and innovative. Retina specialists as a group continue to want to lead. Every retina doctor wants to be innovative and offer patients the newest best therapy that they can, and retina doctors want their patients to do well. We know as a group that the frequent injections that some patients require are typically intolerable over the long term, and that adherence cannot be expected. We all want our patients to do better, and if we have an agent that can do that while reducing the burden of treatment, I’m impressed that most retina specialists would be willing to adopt it relatively early in its commercial life cycle.

Transcript Edited for Clarity