EyePoint Pharmaceuticals' investigational sustained-release therapy EYP-1901 has demonstrated promising results in reducing treatment burden for patients with neovascular age-related macular degeneration (wet AMD) while maintaining visual outcomes comparable to standard anti-VEGF therapy, according to interim data from the phase 2 DAVIO-2 trial presented at recent medical conferences.
Novel Pan-VEGF Receptor Inhibition Approach
EYP-1901 represents a significant advancement in retinal drug delivery, combining the pan-VEGF receptor inhibitor vorolanib with EyePoint's proprietary Durasert-E bioerodible technology. Unlike current anti-VEGF therapies, vorolanib inhibits VEGF receptors 1, 2, and 3 intracellularly while also targeting the PDGF receptor, potentially offering additional benefits in reducing progression to fibrosis. Importantly, the drug does not inhibit the tie-2 pathway, allowing continued vascular stability function.
The Durasert-E delivery system marks an evolution from previous steroid implant technologies, featuring a purely bioerodible matrix that completely degrades after approximately 9 months, leaving no permanent residue in the eye. This contrasts with earlier implant designs that retained a polyamide shell after drug depletion.
DAVIO-2 Trial Design and Patient Population
The randomized phase 2 trial enrolled previously treated wet AMD patients who had received at least two anti-VEGF injections in the six months prior to study entry. All participants first received three loading doses of aflibercept before randomization to either EYP-1901 (2mg or 3mg doses) or continued aflibercept treatment every eight weeks.
The study's 56-week duration allows for comprehensive long-term safety and efficacy assessment, with the current analysis focusing on 32-week interim results. Patients in the EYP-1901 groups could receive supplemental aflibercept injections based on predefined retreatment criteria involving visual acuity changes, hemorrhage presence, and anatomical OCT measurements.
Primary Efficacy Outcomes
The trial met its primary endpoint of non-inferiority in best-corrected visual acuity changes at week 32. Dr. Rishi Singh noted that "best-corrected acuity, which was the primary end point, was stable over 6 months" across all treatment groups. Central subfield thickness measurements showed similar stability, with only approximately 10 microns difference between the aflibercept and EYP-1901 groups.
A notable finding was the consistent anatomical response pattern observed with EYP-1901. Dr. Ash Abbey explained that while "the Eylea group kind of has a sawtooth pattern over the course of the last few months of the trial" due to drug fluctuations between injections, "EYP-1901 has something called zero order kinetics, and so it's constantly releasing the vorolanib over the course of that roughly 9 months that it's in the eye."
Significant Treatment Burden Reduction
The most clinically significant finding was the substantial reduction in treatment burden achieved with EYP-1901. At the 6-month assessment, 64% of patients remained supplemental injection-free, representing a major improvement in treatment convenience for this chronic condition.
The overall treatment burden reduction was even more impressive, with 85-89% fewer injections required compared to the six months prior to study enrollment. Dr. Singh emphasized the clinical importance of this finding, noting that "85% of participants had a mean reduction in treatment burden, compared with the 6 months prior to randomization, which demonstrated the product's ability to potentially reduce the burden of treatment for patients."
Safety Profile and Tolerability
The safety analysis revealed no ocular serious adverse events related to EYP-1901 treatment. The most commonly reported adverse events were vitreous floaters and worsening of AMD, both occurring in low numbers. This favorable safety profile supports the potential for broader clinical application of the sustained-release approach.
Dr. Singh noted that "from the standpoint of safety, we are always concerned about safety overall. And we found essentially that this drug was very safe, there were no ocular, serious adverse events reported related to this EYP-1901 overall."
Clinical Impact and Future Implications
The DAVIO-2 results address a critical unmet need in wet AMD management. Dr. Singh highlighted that "one of the biggest concerns or issues around anti-VEGF therapy is really the burden of treatment" requiring multiple office visits, physician time, and transportation challenges for an aging patient population.
The sustained-release approach could particularly benefit patients who struggle with frequent injection schedules, as real-world studies consistently show that patients receive fewer injections than recommended, leading to suboptimal visual outcomes. Dr. Singh observed that "patients don't get nearly the number of injections in the real world we expect them to get until they fall off the visual acuity curves."
The trial continues toward its 56-week endpoint, with long-term data expected to provide additional insights into the durability of treatment response and extended safety profile. If successful, EYP-1901 could represent a paradigm shift in wet AMD management, offering patients extended treatment intervals while maintaining therapeutic efficacy.
