EyePoint Pharmaceuticals, Inc. has announced the dosing of the first patient in its global Phase 3 LUGANO clinical trial evaluating Duravyu (vorolanib intravitreal implant) for the treatment of wet age-related macular degeneration (wet AMD). Duravyu is an investigational sustained delivery therapy that utilizes EyePoint's Durasert E technology to deliver vorolanib, a selective tyrosine kinase inhibitor (TKI).
LUGANO Trial Design
The LUGANO and LUCIA trials are global, randomized, double-masked, Phase 3 studies designed to compare Duravyu to aflibercept in patients with active wet AMD, including both treatment-naïve and previously treated individuals. Each trial aims to enroll approximately 400 patients who will be randomly assigned to receive either a 2.7 mg dose of Duravyu or on-label aflibercept. Patients in the Duravyu arm will receive an intravitreal injection every six months, beginning in the second month of the trial, following three initial monthly aflibercept injections. The primary endpoint is the average change in best corrected visual acuity (BCVA) at weeks 52 and 56 compared to baseline. Secondary endpoints include safety, reduction in treatment burden, the percentage of eyes free of additional aflibercept injections, and anatomical outcomes measured by optical coherence tomography (OCT).
Potential Impact on Wet AMD Treatment
Wet AMD patients often require frequent injections, leading to a high treatment burden and potential vision loss due to delayed or missed appointments. Duravyu offers a novel mechanism of action as a pan-VEGF receptor inhibitor, targeting all VEGF receptors, and has shown neuroprotective and antifibrotic properties. Data from the Phase 1 DAVIO and Phase 2 DAVIO 2 trials demonstrated clinically meaningful outcomes in wet AMD, including stable visual acuity, central subfield thickness (CST), and a favorable safety profile. In DAVIO 2, Duravyu reduced treatment burden by approximately 88% at eight months, with over 80% of patients either supplement-free or requiring just one supplemental anti-VEGF injection through the eight-month period.
Expert Commentary
Jay S. Duker, MD, president and CEO of EyePoint, stated that the first patient dosed in the LUGANO trial represents a significant milestone for the company and Duravyu. Ramiro Ribeiro, MD, PhD, chief medical officer of EyePoint, noted the enthusiasm for the Phase 3 protocol, which aligns with clinical practice by including active treatment through trial duration. Carl Regillo, MD, FACS, director of Retina Service at Wills Eye Hospital, believes Duravyu has the potential to improve the treatment paradigm for this lifelong disease by maintaining a majority of patients with active disease with no supplemental anti-VEGF therapy for six months or longer.
Ongoing Studies
EyePoint anticipates initiating the LUCIA trial by the end of 2024. Duravyu is also being studied in the Phase 2 VERONA trial for diabetic macular edema (DME), with topline data expected in the first quarter of 2025.
