EyePoint Pharmaceuticals has launched two pivotal global phase III clinical trials – LUGANO (NCT06668064) and LUCIA (NCT06683742) – to assess the efficacy and safety of EYP-1901, a novel sustained-release intravitreal treatment for wet age-related macular degeneration (wAMD). The trials aim to confirm results from the successful phase II DAVIO 2 study (NCT05381948) and offer a long-acting alternative to existing anti-VEGF therapies.
Current standard-of-care therapies for wAMD, such as aflibercept, require frequent intravitreal injections, posing a substantial burden on patients, caregivers, and providers. EYP-1901 is a bioerodible, sustained-release formulation of vorolanib, a selective pan-VEGF receptor tyrosine kinase inhibitor, delivered via Durasert E™ – EyePoint’s proprietary intravitreal insert technology. This insert is designed to provide controlled, therapeutic drug levels for ≥6 months following a single administration.
In DAVIO 2, EYP-1901 met its primary endpoint and demonstrated a favorable safety profile. Notably, 63 percent of patients required no supplemental aflibercept injections during the six months following a single dose of EYP-1901.
Design and methodology
Both LUGANO and LUCIA are multicenter, randomized, controlled phase III trials powered to assess noninferiority of EYP-1901 2.7 mg every six months compared to aflibercept 2.0 mg every eight weeks (q8W). Each trial is expected to enroll approximately 400 patients, encompassing both treatment-naïve and previously treated individuals with wAMD.
All participants will receive three monthly loading doses of aflibercept 2.0 mg. At week 8, patients in the EYP-1901 arm will receive a single intravitreal injection of EYP-1901 2.7 mg, with subsequent doses administered every six months. To preserve masking, patients in this group will also receive sham injections every eight weeks. Meanwhile, patients randomized to the aflibercept arm will continue q8W aflibercept 2.0 mg injections throughout the study.
Beginning at Week 12, supplemental aflibercept 2.0 mg may be administered based on prespecified rescue criteria in both arms.
Study endpoints
The primary endpoint is the difference in mean change in best-corrected visual acuity (BCVA) from baseline to Weeks 52 and 56 (averaged), comparing EYP-1901 to aflibercept q8W.
Key secondary endpoints include:
Proportion of eyes free of supplemental anti-VEGF treatment
Reduction in treatment burden
Anatomical stability
Overall safety and tolerability
Patients will be followed through 96 weeks, providing robust data on long-term efficacy, durability, and safety.
Timeline
The first patient in the LUGANO trial was dosed in October 2024. The outcomes of LUGANO and LUCIA are expected to inform real-world clinical decision-making and support regulatory approval of EYP-1901 as a long-acting treatment option for wAMD. If successful, this could significantly reduce injection frequency and alleviate treatment burden, enhancing adherence and patient quality of life.
These phase III studies represent a critical step in advancing a sustained-delivery paradigm for wAMD – shifting from frequent anti-VEGF injections to biannual therapy without compromising visual outcomes.
