Dilraj Grewal, MD: Development of MNV in Geographic Atrophy in GATHER Trials

Eyes with geographic atrophy (GA) that developed macular neovascularization (MNV) in the GATHER clinical trials experienced a lower GA growth rate when treated with avacincaptad pegol versus sham.

This post hoc analysis, presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting, demonstrated a similar reduction in GA growth as eyes that did not develop MNV in the GATHER1 and GATHER trials.

“What that tells us is, irrespective of the development of MNV with the drug or natural history, visual outcomes are a little bit worse when you develop MNV, but to the shame extent of 1 line,” investigator Dilraj Grewal, MD, Duke Eye Center told HCPLive.

GA and MNV can occur in the same eye in late-stage forms of age-related macular degeneration (AMD). This analysis addressed characteristics of patients and features of eyes with GA that developed MNV across the GATHER clinical trial program.

GATHER1 and GATHER2 were pivotal, randomized, double-masked, sham-controlled, multi-center trials evaluating the safety and efficacy of intravitreal avacincaptad pegol in eyes with GA over 18 and 24 months, respectively.

GATHER1 withdrew patients who developed MNV from the study; GATHER2 continued the study treatment in eyes that developed MNV and provided anti-VEGF treatment. This post-hoc analysis focused on studying eyes that developed MNV in GATHER1 and GATHER2 for patients who received avacincaptad pegol 2 mg or sham.

Across both trials, 57 eyes developed MNV, including 11.7% (n = 34 of 290) in the avacincaptad pegol 2 mg arms and 8.0% (n = 23 of 287) in the sham arms, while 520 did not develop MNV. Demographic data of avaincaptad pegol-treated eyes that developed MNV were similar to study eyes that did not develop MNV, by age, gender, and active smoking status at baseline.

Among study eyes that developed MNV, the GA growth rate over 18 months was 2.57 mm2 for avaincaptad pegol 2 mg-treated eyes and 3.16 mm2 for the sham group (difference, 0.59; 95% CI, –0.15 to 1.32), representing an 18.6% reduction in GA growth with the study drug.

For study eyes that did not develop MNV, the GA growth rate over 18 months was 3.16 mm2 for avacincaptad pegol 2 mg-treated eyes and 3.90 mm2 for those that received sham (difference, 0.75; 95% CI, 0.40 - 1.09), representing a 19.1% reduction in GA growth with the study drug.

“That tells us that there is no loss of efficacy of the study drug, even with the development of MNV,” Grewal told HCPLive. “Overall, this speaks to the safety and efficacy of the drug, and it sheds important light on the complication of MNV, as well as the visual and anatomic outcomes.”

Disclosures: Relevant disclosures for Grewal include Apellis, Genentech, Iveric Bio, Regeneron, and others.

Reference

_{Grewal D. Characterization of Eyes With Geographic Atrophy That Developed Macular Neovascularization in the GATHER Clinical Trials. Paper presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting. Stockholm, Sweden. July 17-20, 2024.}