The following transcript has been edited for clarity.
Michael A. Singer, MD: For today’s Retina Minute, I have the pleasure of interviewing my good friend Nauman A. Chaudhry, MD. Nauman, you recently presented data on aflibercept 8 mg (Eylea HD; Regeneron) in the ELARA study. Can you explain the goal of this study and how it was set up?
Nauman A. Chaudhry, MD: Thank you for giving me the opportunity. The ELARA trial evaluated aflibercept 8 mg at extended dosing intervals and assessed the safety and efficacy of monthly dosing with aflibercept 8 mg in previously treated patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME).
Patients had previously received 3 or more anti-VEGF injections within the 5 months prior to study enrollment for previously diagnosed nAMD or DME. Patients were treated monthly for the first 6 months and then extended according to prespecified disease activity criteria if they met the requirements.
Dr. Singer: Did patients have to have active disease and fluid to enter the trial, or did they just need a history of treatment response?
Dr. Chaudhry: They needed a history of active disease and response to anti-VEGF therapy. At the time of study inclusion, patients with DME had to have fluid. For AMD, patients could be dry but previously treated.
Dr. Singer: How many injections did patients receive, and what was the comparator?
Dr. Chaudhry: It was an open-label study with no control group. Everyone received 6 consecutive monthly injections and then was extended according to the study criteria, which differed slightly between the DME and AMD cohorts.
For neovascular AMD, at the end of 6 months, patients could not have retinal fluid in the central subfield, no new-onset foveal neovascularization or hemorrhage, and no need for interval shortening during the preceding 12 weeks. If those criteria were met, treatment intervals could be extended by 2 weeks. The maximum extension patients could achieve was almost 4 months at year 2.
In DME, central subfield thickness (CST) had to be less than 300 µm on spectral domain optical coherence tomography (SD-OCT), or less than 320 µm on the Spectralis SD-OCT platform (Heidelberg Engineering), with less than a 10-µm increase from the lowest previous CST value and no interval shortening within the prior 12 weeks.
Dr. Singer: What were the results?
Dr. Chaudhry: Right now, we only have the 6-month results. The remaining data are still being evaluated. There was a significant mean change in both best-corrected visual acuity (BCVA) and CST through week 24 in patients with neovascular AMD and DME. Vision continued to improve through 6 months.
In patients with DME, the mean BCVA gain was 3.2 letters at week 24, and patients received a mean of 5.8 injections. At week 24, 36.8% of patients with DME gained at least 5 letters, and mean central thickness decreased by 40 µm.
In the neovascular AMD cohort, the mean BCVA gain was 2.5 letters at week 24, with a mean of 6 injections. At week 24, 32.9% of patients with neovascular AMD gained at least 5 letters. Mean CST decreased by 27 µm.
Dr. Singer: Were there any notable safety findings?
Dr. Chaudhry: Through week 24, ocular treatment-emergent adverse events (TEAEs) were reported in the study eye of 17% and 22% of patients in the neovascular AMD and DME cohorts, respectively. The most common events were subconjunctival hemorrhage, cataract, and vitreous floaters. The incidence of serious ocular events through week 24 was low in each cohort. Three cases of endophthalmitis and 1 case of vasculitis were reported in the DME cohort. A case of endophthalmitis was reported in the neovascular AMD cohort, and no vasculitis was noted.
Intraocular inflammation was reported in 1% of patients in each cohort through week 24. The most common events reported were eye inflammation and iritis. Most cases were treated with topical steroids, and patients did well.
Dr. Singer: These are very interesting data. Given that the study helped support approval of monthly aflibercept 8 mg dosing, how have these findings changed your clinical practice?
Dr. Chaudhry: Clearly, the ELARA trial demonstrated meaningful functional and anatomic improvements with aflibercept 8 mg every 4 weeks in previously treated patients. There was some selection bias because these were patients requiring frequent treatment, many on monthly injections.
To see meaningful improvement in best-corrected visual acuity and central thickness, along with continued visual improvement through the 6-month analysis period, is very encouraging. It gives us an additional tool for managing difficult patients in our clinics.
Dr. Singer: I have a clarifying question—what percentage of patients had previously been treated with different medications before enrollment?
Dr. Chaudhry: Approximately 17% had previously received bevacizumab (Avastin; Genentech), 7% ranibizumab (Lucentis; Genentech), and 12% faricimab (Vabysmo; Genentech). About 23% had been treated with aflibercept 2 mg (Eylea; Regeneron) or aflibercept 8 mg, and 35.3% had received more than 1 agent.
Dr. Singer: Given that this study included a broad patient population, how does that affect your treatment approach going forward?
Dr. Chaudhry: As the number of anti-VEGF options continues to grow, this is another tool in our armamentarium. It is not my first-line treatment. I generally start with aflibercept, and in patients who are not responding adequately, I would consider aflibercept 8 mg or faricimab.
In the real world, we are sometimes required to start with bevacizumab. If that does not work, then that would be my sequence.
Dr. Singer: This study really demonstrated the potential of aflibercept 8 mg to improve vision in hard-to-treat patients. Having more options gives retina specialists additional tools to manage these diseases more effectively. Is there anything else you would like to add?
Dr. Chaudhry: One interesting observation is that improvements in BCVA and CST appeared to continue over time and had not plateaued by 6 months. This is the only trial in which patients received 6 monthly injections. It will be interesting to see the 1-year data. If vision continues to improve beyond 6 months, we may need to rethink our treatment algorithms. That is a very interesting observation from this study so far.
Dr. Singer: Sounds fascinating. We’ll have to stay tuned for the 1-year data. Thank you for sharing the data with us today. It’s exciting information and gives us more flexibility in dosing and treating patients with this medication.
Dr. Chaudhry: Thank you.
