The Phase 3 LUGANO clinical trial is underway, investigating the efficacy and safety of EYP-1901, a sustained-release intravitreal implant, for the treatment of wet age-related macular degeneration (AMD). The trial aims to demonstrate non-inferiority in visual acuity compared to the current standard of care, aflibercept, while significantly reducing the treatment burden for patients. With the first patient dosed, the trial is actively enrolling participants to assess the potential of six-month dosing intervals with EYP-1901.
LUGANO Trial Design and Objectives
The LUGANO trial is designed as a non-inferiority study comparing EYP-1901 to aflibercept. Patients in the control arm receive aflibercept according to the standard regimen: three loading doses followed by every-other-month injections. The treatment arm receives three loading doses of aflibercept, followed by an EYP-1901 implant at the third injection. Both groups are monitored monthly for up to two years, with aflibercept available as a rescue treatment if needed.
The primary endpoint is the change in visual acuity, with a key secondary endpoint being the reduction in treatment burden. EYP-1901 is designed to release medication consistently over six to nine months, potentially allowing for extended dosing intervals. According to Ash Abbey, MD, principal investigator of the LUGANO clinical trial, the goal is to demonstrate that EYP-1901 can maintain visual acuity with significantly fewer injections.
Promising Phase 2 Data
Data from the Phase 2 DAVIO 2 trial have informed the design and expectations for the LUGANO trial. The DAVIO 2 trial demonstrated that a single dose of EYP-1901 was non-inferior to standard aflibercept dosing over a year. Furthermore, the safety profile of EYP-1901 was comparable to that of aflibercept, with no significant differences in adverse events observed across nearly 200 patients.
"Many patients with the implant did not require any rescue injections for about 6 months after treatment in the DAVIO 2 trial," noted Dr. Abbey. This reduction in treatment frequency is a major focus of the LUGANO trial.
Key Outcome Measures and Anatomical Stability
In addition to visual acuity and treatment burden, the LUGANO trial is evaluating anatomical markers such as central subfield thickness and the presence of fluid on optical coherence tomography (OCT). EYP-1901's zero-order kinetic release is expected to stabilize vascular leakage and reduce anatomical fluctuations, which are linked to poorer long-term visual outcomes. The trial aims to demonstrate that consistent EYP-1901 treatment can lead to better long-term visual prognosis by maintaining a dry retina with fewer injections.
Enrollment and Future Expectations
Enrollment in the LUGANO trial has been relatively smooth, particularly among patients who have difficulty maintaining frequent anti-VEGF injection schedules. However, recruiting treatment-naive patients may present a challenge as the trial progresses. The parallel international trial, LUCIA, is also underway.
If the LUGANO and LUCIA trials yield positive results, potential FDA approval for EYP-1901 could be possible within the next three to four years, offering a new treatment option to reduce the burden of frequent injections for patients with wet AMD.
