Phase 3 LUGANO Trial explores EYP-1901’s potential to reduce treatment burden in wet AMD Patients

Ash Abbey, MD, discusses the Phase 3 LUGANO trial for EYP-1901 in treating wet age-related macular degeneration. Abbey discusses the trial’s non-inferiority objectives, treatment schedule, patient outcomes like reduced treatment burden, and anatomical stability. Patient interest is high, particularly among those wanting fewer injections, though recruiting treatment-naive patients may be challenging. If results are favorable, potential FDA approval could occur within 3 to 4 years.

Video Transcript:

This transcript has been lightly edited for clarity.

David Hutton: I’m David Hutton of Ophthalmology Times. The first patient was recently dosed in the Phase 3 LUGANO clinical trial of Duravyu for the treatment of wet age-related macular degeneration. Today, I’m joined by Ash Abbey, principal investigator of the LUGANO clinical trial. First, what are the key points in the latest data from this clinical trial?

Ash Abbey, MD: We have data from the Phase 2 trial, which we can use to guide our approach in the Phase 3 trial. The Phase 2 trial was called DAVIO 2. In that trial, we now have a full year of data showing a significant reduction in treatment burden for patients who received EYP-1901, the implant currently being used in the Phase 3 trial. In terms of safety, in the nearly 200 patients treated with EYP-1901, we haven’t seen any significant differences in adverse events between EYP-1901 therapy and standard injections, such as aflibercept, which was the comparator in the DAVIO 2 trial. So far, EYP-1901 shows a good safety profile. Many patients with the implant did not require any rescue injections for about 6 months after treatment in the DAVIO 2 trial.

David Hutton: Can you explain the main objectives and design of the LUGANO clinical trial, and what distinguishes it from previous studies?

Ash Abbey, MD: The LUGANO clinical trial is primarily a non-inferiority trial. The main goal is to demonstrate a non-inferior change in visual acuity compared with the current standard of care, which is aflibercept, with three loading doses followed by every-other-month dosing. In this trial, the control arm will receive aflibercept in that regimen, while the treatment arm will receive a higher dose of EYP-1901. Patients in the treatment arm will receive 3 loading doses of anti-VEGF injections, specifically aflibercept, and on the third injection, they will also receive EYP-1901. Both groups will then be monitored monthly for rescue treatment needs, with aflibercept available as a rescue option for up to 2 years.

The secondary endpoint is the reduction in treatment burden, which is essential because EYP-1901 might allow for every-six-month dosing, with supplemental anti-VEGF injections only as needed. However, in this trial, EYP-1901 will be administered every 6 months for the treatment group for the full two years.

David Hutton: What are the key patient outcomes being measured, and how will you use these metrics to assess treatment efficacy?

Ash Abbey, MD: A key outcome will be maintaining visual acuity. In the DAVIO 2 trial, we saw that 1 dose of EYP-1901 was non-inferior to standard aflibercept dosing over a year. We hope to see similar outcomes in the LUGANO trial with every-6-month dosing. The reduction in treatment burden while maintaining good visual acuity is crucial.

We’ll also look at anatomical markers, specifically central subfield thickness and fluid on OCT. EYP-1901 is designed to provide zero-order kinetic release, offering a consistent release of medication over 6 to 9 months. This should help stabilize vascular leakage and reduce anatomical fluctuations, which are linked to worse visual outcomes over time. We hope that with consistent EYP-1901 treatment, we may see better long-term visual outcomes.

David Hutton: What unique challenges have you faced during this trial?

Ash Abbey, MD: So far, it’s been relatively easy to enroll patients. Many who have been treated with anti-VEGF injections but can’t go beyond 6 to 8 weeks between doses are eager to reduce their treatment burden. These patients are highly interested in the possibility of only needing an injection every 6 months. However, only 25% of the trial participants will be previously treated patients. Once we reach that limit, we’ll need to recruit treatment-naive patients, which may be more challenging. Still, emphasizing the potential for fewer treatments should help attract participants.

David Hutton: Based on the data collected so far, are you seeing any promising trends or findings?

Ash Abbey, MD: We’re just beginning Phase 3, but in Phase 2 DAVIO 2, we observed promising trends, including a stable central subfield thickness over time, which is a key anatomical marker. In contrast to every-other-month dosing with Eylea, EYP-1901 has shown a more stable trend over 6 months to a year. Achieving dry retinas with fewer injections would be a successful outcome, and reduced anatomical fluctuations may lead to a better long-term visual prognosis.

David Hutton: Lastly, what’s the timeline for LUGANO, and where does it go from here?

Ash Abbey, MD: LUGANO will likely continue enrolling patients over the next year to year and a half. There’s also a similar trial called LUCIA, which will run in parallel internationally. Once enrollment is complete, and with positive results, we might see potential FDA approval in the next 3 to 4 years.