"Efficiency" is a central theme in modern retina practice. With an ever-growing array of treatments for neovascular age-related macular degeneration (nAMD), and two new geographic atrophy (GA) drugs, it is obvious why. However, bringing a personal touch to patient care is paramount for me.
I started a retina clinical trials department at our multispecialty practice, and it has become the most rewarding aspect of my career and easily my favorite part of what I do.
I value the opportunity to impact our field while at the same time providing eligible patients with access to cutting-edge advancements and the chance for better visual outcomes.
Treatment preferences for real-world retina patients
I aim for patients to achieve the best visual acuity possible, and I always aim to improve. At the same time, durability is important, and I want to help patients have the ability to go longer between injections.
Many ask why they need injections more often when “the commercials say I should be getting this every 4 months.” I tell them there is a difference between the commercial and reality, and we must live in reality.
Clinical trials do not reflect real-world clinical practice. Unlike patients who are seen and managed daily, studies involve strict inclusion and exclusion criteria to determine which patients qualify for the study. Clinical trial protocols dictate specific treatment regimens that may not reflect real-world treatment patterns.
Study results from these trials tell us which drugs are effective but do not necessarily help us accurately predict just how effective they will be across a broader population and which regimens are best for each individual patient in clinical practice.
Dr. Danzig’s prescribing preferences for treatment-naïve patients
I commonly begin patients on AVASTIN (bevacizumab, Roche) off-label while waiting for insurance approvals. If insurance allows, I can start a treatment-naïve patient on a branded medication (or use a sample). My preference is VABYSMO (faricimab sova; Genentech) or EYLEA HD (aflibercept; Regeneron), and I can treat them almost like a clinical trial patient.
My philosophy is if I'm able to start these treatment-naïve patients on one of these two medications, I'll do it. In general, for patients that I begin on AVASTIN, I try to switch to a more durable therapy, and I do believe branded medications provide better disease control.
When it comes to GA, I am injecting both SYFOVRE (pegcetacoplan; Apellis Pharmaceuticals) and IZERVAY (avacincaptad pegol; Astellas). In light of concerns regarding vasculitis with the former,1 I start new patients on the latter based on safety.
Patients requiring both GA and nAMD treatments add complexity to the practice's flow. It is certainly a challenge to keep up the intervals; life does get in the way, and patients miss shots for a variety of reasons. Therefore, optimizing the management of our nAMD patients to achieve the best vision outcomes possible, along with the longest-lasting agents, is paramount.
Setting patient expectations for retinal disease treatments
Setting patients' expectations is so important in medicine and this is particularly true for retinal conditions. Whether patients have nAMD or dry AMD, there is no cure; instead, the therapies help treat the symptoms of these diseases.
When I discuss this with patients, I tell them we have excellent treatments available. For nAMD patients, we have been doing these injections for 18 years now and have come a long way from the time when all patients lost vision before the advent of anti-vascular endothelial growth factor (VEGF) intravitreal injections. The goal at that time was to prevent significant vision loss.
I tell them today that patients commonly gain vision. However, I do not know which drug or how many injections one may need; many patients require injections as frequently as every 4 to 6 weeks. The good news is that we have medicines we can switch to that may act longer once we determine what their insurance covers.
Although many different FDA-approved drugs are available to treat nAMD, they all demonstrate a similar and comparable degree of vision gain.
Patient conversations on GA treatments
For patients with dry AMD, the conversation generally happens over multiple visits with a significant amount of chair time involved. I tell them, “How you see today is the best you will see for the rest of your life.” It’s a sobering conversation for many patients, but I also say that 2023 was a landmark year.
For the first time, two medications have been approved for this condition. With this newly available treatment, we aim to maintain your vision so you can maintain your independence for as long as possible.
I tell them the medications are meant to slow the progression of GA; however, there are some side effects, and developing nAMD is one possibility. Yet, we now have an opportunity to treat something we could not before. There is no "wow" for patients with GA treatment, and there is no way to measure the rate of progression.
When patients ask how they are doing, the best I can do is assure them they have not developed wet AMD, there's no inflammation, and their vision is stable—which is the goal of GA treatment. In my experience, patients at risk of going blind are motivated to do anything they can to maintain their vision.
Can we achieve better visual outcomes with current retinal disease treatments?
As mentioned earlier, real-world patients do not always have the same visual acuity results as clinical trial patients. In one study using real-world data from the IRIS Registry, researchers analyzed standard-of-care anti-VEGF treatment patterns over 6 years.2 They found patients were undertreated and losing vision in the long term, below where they started.
Although they experienced a mean visual acuity increase of 3 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at year 1, this was followed by annual decreases, leading to a net loss from baseline of 4.6 letters after 6 years. As far as we have come, we can and should do better.2
Despite this unmet need for better vision, most agents in late-stage development for nAMD want to increase durability with longer intervals between injections and not superior visual outcomes.
Developments in retinal disease treatments
Opthea's sozinibercept, a novel potent trap fusion protein that inhibits VEGF-C and VEGF-D, is the only exception. Robust (n=266) phase 2b data demonstrated patients assigned combination treatment with 2mg sozinibercept plus 0.5mg ranibizumab (n=123) achieved the primary endpoint of a significant mean change in best-corrected visual acuity (BCVA) from baseline to week 24 of +14.2 letters.3
This represents an additional gain of +3.4 letters (P = 0.0107) over the ranibizumab plus sham control group. Even greater gains in VA were achieved over the control group in pre-specified analyses of patients with specific lesion sub-types, including the polypoidal choroidal vasculopathy (PCV) sub-population.3
Sozinibercept is now being studied in two fully-enrolled global phase 3 registrational trials, ShORe and COAST, which are evaluating the investigational agent in combination with 0.5mg ranibizumab (Lucentis; Genentech) and 2mg aflibercept, respectively.4
In addition, phase 3 clinical trials are underway for nAMD to explore other dual-target agents, gene therapy, tyrosine-kinase inhibitors, and alternative pathways. ATMOSPHERE and ASCENT are evaluating RegenexBio Inc.'s subretinal gene therapy ABBV-RGX-314. The NAV AAV8 vector encodes an antibody fragment designed to inhibit VEGF-A as a single surgical subretinal injection performed in an operating room setting.5
SOL-1 is evaluating Ocular Therapeutix's bioresorbable, hydrogel implant incorporating the tyrosine-kinase inhibitor axitinib.6 The DAYBREAK study will include Kodiak Sciences' KSI-501, an anti-interleukin 6 (IL-6) and VEGF trap bispecific antibody biopolymer conjugate, and tarocimab tedromer, which is an anti-VEGF biologic designed for long-interval dosing.7
Conclusion
The bottom line is that we retina specialists will do whatever it takes to provide patients with the best visual acuity possible.
Whether it is a potentially “one-and-done” gene therapy procedure or treatment with a combination of agents, the future of our patients' developing age-related retina diseases has never been more promising.
