For this month's Retina Minute, I have the opportunity to talk to my dear friend, Dr. Veeral Sheth, who is partner and director of clinical trials at University Retina in Illinois and clinical assistant professor at the University of Illinois at Chicago.
Dr. Sheth, you presented some fascinating data at EURETINA about the AVONELLE-X clinical trial for the use of faricimab (Vabysmo, Genentech) in patients with wet macular degeneration (AMD). Can you tell us about the study design and the findings?
First, Dr. Singer, thanks for having me. It was a privilege to present this data from the largest extension trial in neovascular AMD to date. We were able to show long-term results in how patients who have been on treatment for 4 years (ie, patients who were in the original TENAYA and LUCERNE studies and then had 2 years of further treatment with faricimab) do on the treatment with fewer and fewer injections over time.
In short, their BCVA, anatomy, and central subfield thickness findings remained stable over the course of that third and fourth year into the extension. These patients received faricimab in a treat-and-extend fashion, and the median number of injections was about 7 in those last two 2 years. This result is quite different than what we have historically seen in the real world with precipitous declines in vision in years 2, 3, and beyond of treatment. This trial gives us hope that we can bridge that gap between clinical trial and real world data with more durable and longer-acting treatments.
The other interesting thing we saw was for patients who ended the TENAYA and LUCERNE studies on aflibercept (Eylea, Regeneron): 152 of those patients who received Q8-week dosing still had persistent retinal fluid, but when they switched to faricimab in years 3 and 4, we saw 44% fewer patients who still had fluid at the end of the fourth year. These results tell us that even our more difficult to treat patients can see the benefits from switching to a medicine like faricimab. That may be related to the dual mechanism of action, which is different from our standard anti-VEGF treatments.
How far were patients allowed to be extended in the AVONELLE-X trial, and what percentages of them fell into the different buckets?
The maximum extension in this trial was 16 weeks, and more than 60% of patients at the end of year 3 and at the end of year 4 were able to achieve that interval. If you were to take the treat-and-extend criteria and apply it to these patients, more than half would have theoretically gotten to a 20-week interval, which again confirms that these treatments do last quite a while for a large number of our patients. I believe we will start seeing newer trials that look beyond 20 weeks and 24 weeks as a result of AVONELLE-X.
Were there any safety concerns in either group during the third and fourth years of this trial?
We focused primarily on whether the safety signals in the parent studies, TENAYA and LUCERNE, were similar to what we saw in the extension, and we found that faricimab was still well-tolerated and its safety profile was consistent with what we saw in those parent studies. More specifically regarding adverse events, we saw a clean safety profile in the parent studies and no cases of occlusive vasculitis in AVONELLE-X.
Was the change in visual acuity from year 2 to year 4 a gain or a loss of letters?
Vision remained stable. Baseline in the parent trials before patients received any injections was about 61 letters, and at the end of TENAYA and LUCERNE, we saw that those patients were at about 65.8 letters. Then, carrying forward to the end of year 4, patients were at about 63.8 letters. We know that with any treatment, there is always a slight decline—it is the nature of the degeneration—but the fact that they stayed right in that 63- or 64-letter range was great to see.
From the anatomy standpoint, one of the things that we always worry about with chronic anti-VEGF use is the development of macular atrophy. Was that studied in this trial, and does it explain why there is a slight change in visual acuity over time?
That has not been looked at in this trial yet, but this is just the first presentation of the data, so I believe that it will be analyzed more closely in the future.
How do the data from second-generation medications change your outlook in how you approach your patients with wet macular degeneration?
One of the things we saw in this trial was that patients maintained good vision if they came in with good vision. For example, 20/40 vision patients were enrolled, and at the end of 4 years, 75% of them remained 20/40 or better. You and I both know that, in the real world, we have not seen data like that, perhaps because we undertreat our patients outside of trials. However, knowing that patients maintained good vision after 7 total injections in years 3 and 4 of AVONELLE-X encourages me to start addressing the drag on vision over time that we have seen in the real world. When I counsel my patients, I say, "If we are able to address your issue in a timely fashion and we do what we need to do in terms of treatment and frequency of treatment, then there is a good chance we can keep you seeing well and doing those things that you want to do. 20/40 vision is driving vision. It is the ability to see your kids' or grandkids' faces."
This is great data, and it helps affirm the fact that second-generation medicines are good not only for the short-term but also for the long-term. The dual mechanism of action seems to both anatomically and visually keep the eye stable, which is what we have been hoping for since HORIZON and other long-term trials that showed patients’ vision declined if the injections stopped. It is heartening to see as we treat these patients for longer and longer periods of time.
Thanks for being here, Dr. Sheth.
Thanks again for having me.
This editorial content was supported via unrestricted sponsorship.