Jay Duker, MD, president and CEO of EyePoint, spoke with Ophthalmology 360 about two phase 3 trials currently enrolling for wet age-related macular degeneration (AMD).
Question:
Can you give an update on the clinical trials assessing DURAVYU for the treatment of wet age-related macular degeneration?
Jay Duker, MD:
DURAVYU is our lead asset. The trials are both going very well, but let me take a step back. It is a combination of the small molecule tyrosine kinase inhibitor called vorolanib, that is in our next-generation sustained delivery technology called Durasert-E. We’ve already studied DURAVYU in a phase 1 and three phase 2s, so we have quite a bit of efficacy and safety background on DURAVYU in humans. In fact, we’ve placed DURAVYU in over 190 patients with favorable safety profile across those 4 clinical trials.
We’re currently in phase 3 in two clinical trials, the LUCIA trial, which is the most recent to fully enroll. But we also had full enrollment in a prior trial called the LUGANO trial, which fully enrolled at the end of May this year. Both of these trials are identical. We enrolled over 400 patients in each trial. They are patients who have wet age-related macular degeneration, either previously treated or treatment-naive. We expected to enroll a ratio of about 75% to 25% naive versus previously treated. That’s the ratio we achieved in both these trials.
One of the remarkable things about our enrollment is it went really, really fast. We enrolled each trial in about 7 months, which to our knowledge, is the fastest enrollment of any wet AMD trial ever. What we attribute this to first of all is we have this really good, strong, large data set from our previous trials showing that DURAVYU appears to be safe and efficacious.
That gives the investigators a lot of comfort in asking their patients to enroll in a trial. Of course, when the patients hear about the previous experience with DURAVYU, that also gives them comfort that this product appears to be safe and effective. The other reasons we were able to enroll so quickly is this is what I call a tried and true approach to approval in wet age-related macular degeneration.
Both of these trials, the LUGANO and LUCIA, are the primary endpoint is change in best corrected visual acuity compared to an on-label Eylea control, and it’s a non-inferiority trial set up. The last 4 approvals in wet AMD have been non-inferiority trials. Physicians, even the ones who are not participating in the trial, really understand what the non-inferiority trial means. Given that our control group was on-label Eylea, meaning 3 monthly injections of Eylea followed by every other month, I think the results should they be positive, will be very easy for the retina community to understand.
One last note about how the trial’s going. We did report just a few weeks ago that our data safety monitor committee had met and they saw the mass safety data and recommended no changes in the protocol. Again, that’s important. Our protocol has really been the same that we started with when these trials first started enrolling.
We haven’t made any significant changes, which is de-risking of course, and also I think illustrates how much we learned from our phase 2 program. To summarize, how are things going? Couldn’t be going better. We are delighted with the enrollment. We are delighted with the mass safety results that we’ve seen so far. That’s the primary endpoint.
Both trials, the LUGANO and the LUCIA trial, are both 2-year trials. The second year is for safety because we’d like to see a label that allows doctors to re-inject our drug unlimited to wet AMD patients, really for as long as they need it or perhaps for the rest of their lives. With that in mind, in these trials, we’re re-injecting our drug DURAVYU every 6 months. Primary endpoint is change in visual acuity compared to the Eylea control in a non-inferiority basis. The non-inferiority margin that the FDA has granted for this trial is minus 4.5 letters, which is a standard non-inferiority margin.
The other important endpoint is safety. Again, in the retina community, safety really is paramount. We’ve seen that in some other drugs that have been approved but perhaps have not done as well in the retina community due to some safety concerns. So far, again, as I mentioned, our safety has really been really very clean.
The other endpoint, which is a secondary endpoint, which we believe will be important, is the reduction in the treatment burden. Now, what that means is how many injections did the Eylea patients get over the 1 or 2 years of the trial versus how many injections did the DURAVYU patients get? We’re trying to keep the vision stable or perhaps even improve it in the long term using DURAVYU. But what we’d also like to show is we can do that with fewer visits and fewer injections. That would be another important endpoint for us to show in the trials.
Question:
How might this potential therapeutic option impact the wet AMD space?
Jay Duker, MD:
The first trial, the LUGANO trial, finished enrollment at the end of May. The primary endpoint is at week 56. We’ll get the data sometime early toward the middle of the summer next year in 2026. It will take several weeks for us to analyze the data, but we expect to make public announcements about the top-line data from the first trial mid-summer next year, 2026.
The second trial is only approximately 2 months behind. The second trial, the LUCIA trial, should read out late summer, early fall of 2026. We’re really excited because essentially the countdown has started. We’re under 1 year for top-line data from the trial, and we’re very excited for the results. Based on the excellent phase 2 results we got, we’re confident in the results. The obvious impact I did touch on, which is this reduction in treatment burden.
We have some very good treatments for wet age-related macular degeneration. They all work through the same mechanism of action. Even though we’ve had some recent approvals that have the ability to take some patients out longer between injections, we’re still injecting on average about every 2 months. That’s really for the rest of the patient’s life. I think patients and physicians would welcome the opportunity to extend those intervals out even longer in some patients, maybe not all, but in some patients.
We hope that if we can match or improve on the phase 2 results, we would expect and hope to get FDA approval and then become part of the physician’s armamentarium to allow them to take patients out longer between visits and shots. However, we think there’s other potential long-term benefits here. We do know wet age-related macular degeneration in the long-term, even when patients can keep up with the visits, often results in decreased vision in the long-term.
We think that’s largely due to under-treatment, and it’s not necessarily deliberate under-treatment, but you can imagine, it’s very hard for elderly patients to keep up with the schedule of visits. Sometimes it’s hard for the physicians. Many of my colleagues are doing dozens and dozens of injections every day. It’s a difficult situation. We believe that with a sustained-release insert like DURAVYU that’s releasing drug at a constant level using, what are referred to as your order kinetics for at least 6 months and up to 9 months with each injection, that we hope to show in the long term that we can get better visual acuity results.
There are a couple other potential benefits. One of the other benefits is vorolanib, while it blocks all the VEGF receptors and therefore should block all isoforms of VEGF, it also blocks PDGF, which is responsible for fibrosis.
One of the reasons wet AMD patients lose vision in the long term is fibrosis. We may have a benefit there. Finally, we’ve got some pre-clinical data that we published showing that vorolanib may be neuroprotective, and we show that in a rodent retinal detachment model. Once again, if that’s something that we can show in humans, I think it would be a strong argument that virtually all patients should be treated with DURAVYU if there’s neuroprotection that occurs.
EyePoint has been around for several decades, and we really are the leader in sustained-release drug delivery for retinal disease. We’ve had 4 FDA-approved products using our Durasert technology, and the next-generation Durasert-E is an improvement on that. The inserts are now 94% drug, only 6% matrix, which is a very high drug payload. These inserts also can be shipped and stored at room temperature, which is, we hope to be a very good commercial improvement.
As you may know, all the current wet AMD treatments have to be refrigerated. Retina specialists have very large refrigerators right now. I think they welcome the opportunity to have a new drug that doesn’t have to be refrigerated. Also, our inserts contain no PEG and no PLGA, and those are components of other products that have been associated with some potential toxicity in the eye. We don’t have that.
Finally, what I’m really most proud of is what a great job our team has done. We dosed the first patient with DURAVYU in January of 2021, and here we are about four and a half years later, having fully enrolled 2 pivotal trials in wet age-related macular degeneration. It’s just been an exceptional run of our people at EyePoint, problem-solving together as a team, making great improvements in the product, and being able to shorten all our timelines while actually de-risking the program not increasing the risk.
It’s been a wonderful 4 years, and as I said already, we are really, really optimistic about the results that we’re going to see next summer.
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