Advancements in the treatment of neovascular (wet) age-related macular degeneration (AMD) are focusing on reducing the frequency of intravitreal injections and targeting a broader spectrum of the VEGF family. Recent presentations at the Retina Society and EURETINA Congress highlighted promising results from clinical trials evaluating novel therapies with different mechanisms of action. These include gene therapy, tyrosine kinase inhibitors, and VEGF-C/D inhibitors, all aimed at improving patient outcomes and reducing treatment burden.
Gene Therapy with 4D-150
David A. Eichenbaum, MD, presented interim results from the PRISM Phase 1/2 trial, which is evaluating intravitreal 4D-150 in adults with neovascular AMD. The Phase 2 interim results, focusing on the 3E10 dose, demonstrated that 4D-150 was safe and well-tolerated, with no serious ocular adverse events or clinically significant inflammation. All patients completed a prophylactic topical corticosteroid regimen on schedule. Importantly, the study showed durable clinical activity, with an almost 90% reduction in the annualized anti-VEGF injection treatment burden, stable visual acuity, and sustained reduction in central subfield thickness (CST) stabilization. A Phase 3 trial, informed by these results, is scheduled to begin in early 2025.
Tyrosine Kinase Inhibition with EYP-1901
Dr. Eichenbaum also presented 12-month results from the DAVIO 2 trial, a Phase 2 multicenter study comparing a single injection of EYP-1901 (vorolanib intravitreal insert) with aflibercept in patients previously treated for wet AMD. The DAVIO 2 trial, the largest intravitreal tyrosine kinase inhibition trial to date, demonstrated stable maintenance of visual acuity and strong anatomic control. Half of the EYP-1901 patients were supplement-free, and EYP-1901 reduced treatment burden by 80% compared to pretrial treatment. The therapy was well-tolerated, with no serious ocular or systemic adverse events related to the drug and no intraocular inflammation related to retinal vasculitis or severe drug-related adverse events. A Phase 3 trial is set to commence in the second half of 2024, based on these Phase 2 findings.
VEGF-C/D Inhibition with Sozinibercept
Timothy L Jackson PhD, MB ChB, FRCOphth, discussed research on inhibiting VEGF-C and -D in addition to VEGF-A. Current treatments for wet AMD primarily target VEGF-A, leading to a reciprocal increase in VEGF-C. Sozinibercept is an adjunctive treatment given in conjunction with ranibizumab or aflibercept to target the broader VEGF family. Phase 2b studies showed superior visual acuity compared to ranibizumab monotherapy. Large Phase 3 trials (COAST and SHORE) are underway, combining OPT-302 with ranibizumab in one trial and aflibercept in the other, involving almost 2,000 patients. If Phase 2b results are replicated in Phase 3, sozinibercept could offer patients improved acuity rather than just fewer injections.
Implications for Future Treatment
These advancements represent a significant step forward in the treatment of wet AMD. The potential for reduced injection burden with gene therapy and tyrosine kinase inhibitors, along with the promise of improved visual acuity through broader VEGF family inhibition, could transform the treatment landscape for this prevalent condition. As these therapies advance through clinical trials, they offer hope for more effective and convenient treatment options for patients with wet AMD.
