What LUGANO and LUCIA could signal for DME: Pieramici on the EYP-1901 program

Dante Pieramici, MD, of California Retina Consultants, framed the sustained-delivery tyrosine kinase inhibitor (TKI) EYP-1901 as a potential answer to one of the most persistent problems in retina practice: the burden of frequent intravitreal injections in diabetic macular edema (DME). Speaking as the phase 3 COMO and CAPRI trials completed enrollment, he explained why the drug's inclusion of both treatment-naive and previously treated patients matters for interpreting the data to come.

Pieramici said the earliest beneficiaries are likely to be the field's backlog of previously treated patients—those who never reached full resolution of their edema, who struggle to keep up with frequent injection visits, or who disappear from care for stretches at a time. Because the trials enrolled previously treated eyes, he noted, an eventual approval could carry a broader range of indications and give the community more confidence using the therapy in patients who have already been on anti-VEGF treatment. For treatment-naive patients, he anticipated a shift in approach: clinicians would likely establish a response with one to several anti-VEGF injections—patients in the EYP-1901 arm receive 3 intravitreal aflibercept injections as part of the protocol—before layering the insert on top to reduce the need for supplemental treatment over the subsequent 6 months.

Related video: EYP-1901 in DME: Dante Pieramici, MD, on the COMO and CAPRI phase 3 trials

A recurring theme was the value of durable, low-level suppression. Drawing an analogy to the Port Delivery System refilled every 6 to 9 months, Pieramici said an underlying drug reservoir lasting 6 months, and potentially longer in some eyes, offers "wiggle room" in managing patients whose disease might otherwise worsen if they miss visits.

On the multi-mechanism rationale, Pieramici distinguished what is known from what remains theoretical. Blocking VEGF downstream at the receptor level, inhibiting PDGF—relevant to retinal pericytes and potentially more so in diabetic than in AMD eyes—and interrupting IL-6 JAK/STAT inflammatory signaling that drives vascular permeability beyond the VEGF pathway all make biological sense, he said, and preclinical modeling with vorolanib supports IL-6 inhibition. But he cautioned that isolating the contribution of each mechanism in a clinical trial will be difficult and may require additional study, including comparisons with anti-VEGF and bispecific anti-VEGF/IL-6 approaches.

Related reading: DURAVYU misses primary endpoint in first pivotal wet AMD trial; secondary durability signals hold

Looking ahead to top-line DME data expected in Q4 2027, Pieramici pointed to the wet AMD LUGANO and LUCIA trials as the nearer-term signal for safety, tolerability, and 6-month durability—while stressing that DME is a distinct disease process and efficacy may not translate directly. That caution proved timely: on August 17, 2026, EyePoint reported that LUGANO missed its prespecified primary visual acuity endpoint versus aflibercept, though the insert showed a reassuring safety profile and secondary durability signals, including a 42% reduction in treatment burden and 54% of patients remaining supplement-free through week 56.¹

References

1. Filkins, K. DURAVYU misses primary endpoint in first pivotal wet AMD trial; secondary durability signals hold. Modern Retina/Ophthalmology Times. Published August 17, 2026. Accessed August 24, 2026. https://www.ophthalmologytimes.com/view/duravyu-vorolanib-lugano-phase-3-wet-amd-primary-endpoint