Ladies and gentlemen, thank you for standing by. Welcome to EyePoint LUCIA topl ine data readout. At this time, all participants are in a listen-only mode. Please be advised that today's conference is being recorded. I would now like to hand the conference over to Dr. Jay S. Duker, President and Chief Executive Officer of EyePoint. Please go ahead.
Thank you. Good morning, everyone, and thank you for joining us. Earlier this morning, we issued a press release announcing top-line results from our phase III LUCIA trial evaluating DURAVYU in wet age-related macular degeneration. As a reminder, DURAVYU was designed as a differentiated, sustained-release, multi-MOA TKI to improve the current standard of care in wet AMD, the largest retinal disease market that has been dominated by monotherapy anti-VEGF biologics. Across its clinical development program, DURAVYU has consistently demonstrated meaningful visual and anatomic outcomes, along with a favorable safety and tolerability profile, representing a compelling value proposition for retinal disease physicians and patients. Before we get into the data, I want to first acknowledge what I'm sure is top of mind for many of you. As we disclosed in today's announcement, the LUCIA trial did not meet the primary endpoint despite demonstrating visual improvement through week 56.
We are deeply disappointed by this outcome, given the promising scientific rationale and prior clinical program. We sincerely thank the patients, caregivers, clinicians, and study teams who participated. LUCIA is a randomized, double-masked, aflibercept-controlled non-inferiority phase III trial that randomized over 400 patients, one- to- one, to receive either DURAVYU 2.7 mg or an on-label 2 mg aflibercept control. The trial enrolled both previously treated and treatment-naïve patients with active wet AMD, and along with LUGANO, is the only sustained release wet AMD pivotal phase III study designed to evaluate six-month redosing over two years against the gold standard of care on-label aflibercept. Patients in the DURAVYU 2.7 mg treatment arm received an intravitreal dose of DURAVYU every six months, while patients in the control label arm received on-label aflibercept every two months after the loading phase.
DURAVYU is delivered via standard intravitreal injection in the physician's office, similar to current standard practice with FDA-approved anti-VEGF treatments. The primary endpoint of LUCIA is the average change in best-corrected visual acuity at weeks 52 and 56 blended versus baseline vision. Secondary endpoints include safety, reduction in treatment burden, percentage of eyes free of supplemental aflibercept injections, and anatomical results as measured by optical coherence tomography. With that, let's discuss the topline results in further detail. These are our legal disclaimers. This slide represents the overview of the DURAVYU development program. We have active phase III programs in wet AMD, LUGANO and LUCIA. In DME or diabetic macular edema, we have two active phase III studies, COMO and CAPRI. Today, we will be discussing the results of the LUCIA program. As a reminder, DURAVYU has many potential advantages.
Favorable safety profile, clinically relevant to trial design against on-label standard of care dosing. A potential multi-MOA advantage with the only TKI that combines VEGF receptor blockade and IL-6/JAK1 anti-inflammatory results as well as PDGF potential anti-fibrotic benefit. Durasert is a proven delivery technology with four FDA prior-approved products using similar sustained release. Each DURAVYU insert is 94% drug. There is no PEG or PLGA, and it features room temperature storage. This slide summarizes the results of the LUCIA trial. LUCIA did not meet the primary endpoint of mean change in best-corrected visual acuity despite visual improvements. There was a meaningful reduction in treatment burden with strong anatomic control demonstrating activity of DURAVYU. We showed continued favorable safety profile with redosing. We will be doing additional analyses that are ongoing to assess the next steps for DURAVYU as a potential treatment for wet AMD.
EyePoint is now focused on our DME program, with ongoing pivotal trials that feature a topline data readout in the fourth quarter of next year. Both LUGANO and LUCIA followed an established non-inferiority regulatory pathway for wet AMD. There were a total of 432 patients enrolled in LUGANO and 475 in LUCIA. In each study, there was a one-to-one randomization between DURAVYU 2.7 mg and on-label aflibercept. DURAVYU was dosed every six months, and the primary endpoint was at approximately one year for both safety and efficacy and potential NDA submission. Once again, the primary endpoint was non-inferiority in mean change in best-corrected visual acuity from day one to a blend of week 52 and week 56, with a non-inferiority margin of minus 4.5 letters. There were key secondary endpoints to be evaluated as well.
This schematic slide shows the outline of both LUGANO and LUCIA trials, highlighting the every six month dosing of DURAVYU and the blended endpoint. The baseline characteristics for this study were well-matched, as you can see on this slide. The best corrected visual acuities were approximately 65 letters. Central subfield thickness on OCT was approximately 315 microns in both trials, and the total area of the choroidal neovascularization on fluorescein angiography was 5.8 mm squared versus 5.4 mm squared in the control arm. This slide shows the topl ine result of the primary endpoint mean change in best corrected visual acuity. You can see, at the end of the trial, the DURAVYU arm, on average, gained 2.5 letters, where the difference was minus 3.7 letters, and that was outside of the non-inferiority margin.
With respect to reduction in treatment burden, on average, after the load, the DURAVYU eyes received 3.3 injections, which included two DURAVYUs and 1.3 supplements. The aflibercept arm, on average, after the load, received 5.3 injections. This represents a 38% reduction in treatment burden and if approved, could potentially result in two fewer injections on average against Eylea. For supplement-free, up to week 32, which is approximately six months after the first DURAVYU was delivered, 70% of the DURAVYU patients were supplement-free, 94% had received zero or one supplement, and over 99% had two or fewer supplements. At the primary endpoint, the supplement-free rate was 52%, with 71% patients receiving zero or one supplement, and 83% of the patients had four injections or less at the end of the trial. The anatomic control was good.
As you can see in this graph, against aflibercept at the end of the trial, there was approximately 16 micron difference, which in clinical practice would likely not be felt to be significant at all. If you recall, the difference in the first trial, the LUGANO trial, was approximately 4 microns. So overall, in both trials, DURAVYU showed quite strong anatomic control. From a safety perspective, there were no reported cases of insert migration into the anterior chamber, anterior chamber opacities, free-floating drug particles, or retinal vasculitis. There were AEs of particular interest that occurred in less than 1% in both arms, including intraocular inflammation and endophthalmitis. There was more floaters in the DURAVYU arm than the control arm, but the majority of these cases were mild.
There was a low patient discontinuation rate in both arms of approximately 8%, and none of the discontinuations were due to study or treatment. This slide shows the AEs that occurred greater than equal to 2%, again, highlighting that there were an increased number of vitreous floaters in the DURAVYU arm, similar to what was seen in the LUGANO trial. The pooled results of the reduction in treatment burden showed an overall 40% reduction when the LUGANO and LUCIA trial were pooled together. Again, this could show a potential for two fewer injections per year in wet AMD patients. This slide shows the pooled anatomic data between the two trials, showing a difference of about 10 microns and relatively stable control of the fluid by DURAVYU. This slide is the pooled safety. A total of 443 patients treated with DURAVYU, showing no safety concerns.
I'd now like to review our diabetic macular edema or DME program. COMO and CAPRI are identical phase III DME trials. This was informed by a positive phase II VERONA trial and aligned with both the FDA and EMA on an established non-inferiority regulatory pathway. There was very high physician enthusiasm for participation in the trial, and over 550 patients were enrolled across both trials. The first patients were dosed in both trials in February of this year, and full enrollment was achieved by July. We expect topline data in the fourth quarter of 2027. This is the schematic for the COMO and CAPRI trial. Similar to LUGANO and LUCIA, with two notable exceptions. The first being that on-label aflibercept for diabetic macular edema includes five monthly loading injections.
In addition, in this trial, we dosed DURAVYU on day one in order to show a potential more rapid reduction in fluid and improvement in vision by week four. That decision was influenced by the results of the VERONA phase II trial in DME. As you can see, the purple line representing the DURAVYU arm at week four had increased improvement in vision versus aflibercept, with a concomitant reduction in fluid noted as early as week four. At the end of the trial, without a single outlier patient that missed visits, there was approximately 10 letter improvement in vision in the DURAVYU arm versus 7.3 letters in the control arm, and this was also matched by increased reduction in fluid.
Macular leakage on fluorescein angiography is a biomarker of vascular instability, and there was a dose-dependent reduction in vascular leakage as determined by the reading center on fluorescein angiography, with the DURAVYU arm showing significantly less leakage at the end of the study. This is one of the patients from the 2.7 mg arm in the phase II DME trial. This patient had been treated with monthly injections leading into the trial, first with bevacizumab and later with faricimab. After the washout period, the patient had residual fluid in the macula with a CST of 336 microns and a best-corrected visual acuity of 72 letters. This patient received a single injection of aflibercept along with DURAVYU on day one and received no supplements. At the end of the trial, six months later, the best-corrected visual acuity had improved to 80 letters, and the CST was stable.
So, in summary, LUCIA did not meet the primary endpoint of mean change in best-corrected visual acuity despite visual improvement. There was a meaningful reduction in treatment burden with strong anatomic control and a continued favorable safety profile with redosing. We will be doing additional analyses to assess the next step for DURAVYU as a potential treatment. However, the company is now fully focused on our DME program, with data readout in 4Q of 2027. To close, I want to reiterate that we continue to believe TKIs have the potential to be the next phase of retinal disease innovation. Today's data reinforces our fundamental conviction in DURAVYU. Today's results are supportive of DURAVYU's activity in controlling fluid and reducing treatment burden for patients, as well as the safety of DURAVYU with redosing.
We plan on continuing to review the data from LUGANO and LUCIA to determine the appropriate next steps for DURAVYU in wet AMD. We remain focused on advancing DURAVYU in the phase III program for the treatment of diabetic macular edema, which represents the second-largest retinal disease market and where DURAVYU still remains the only TKI in phase III development. With the multifactorial and inflammatory nature of DME, the potential anti-IL-6 properties of DURAVYU, as well as compelling results in our phase II VERONA study, make us confident that DURAVYU is positioned well to deliver potentially earlier benefits with fewer injections versus the standard of care. We are on track to deliver topline data for our phase III DME program in the fourth quarter of 2027. Most importantly, our commitment to patients in the retina community remains unchanged.
We will continue to follow the data and advance our development programs with the goal of delivering meaningful new treatment options for patients with serious retinal diseases. I'd like to thank the entire EyePoint team for your unwavering commitment to improving the quality of retinal care for the patients we serve. I also want to express our sincere gratitude to the patients, study coordinators, and clinical investigators who have been part of LUCIA and whose partnership has been vital to our growth and success as a company. Thank you for your attention.
Ladies and gentlemen, this concludes this call for the EyePoint phase III LUCIA top line data readout. You may now disconnect from the call.