4D Molecular Therapeutics announced positive long-term data from the phase 1/2 PRISM clinical trial evaluating 4D-150 in patients with wet age-related macular degeneration. The intravitreal gene therapy demonstrated consistent visual acuity maintenance and sustained treatment burden reduction through up to 2 years of follow-up.

In the phase 2b recently diagnosed subgroup most comparable to the phase 3 population, patients experienced a 94% reduction in supplemental anti-VEGF injections through year 1 and 92% through year 1.5 compared to projected standard dosing. The broader phase 2b cohort showed 83% and 82% reductions at the same timepoints. Patients with severe, recalcitrant disease in the phase 1/2a cohort maintained 83% reduction through year 1 and 79% through year 2 compared to their prior year’s injection frequency.

All cohorts demonstrated consistent dose response favoring the phase 3 dose of 3E10 vg/eye versus the lower dose. Visual acuity remained stable through up to 2 years, with consistent control of central subfield thickness on OCT.

Among 71 patients receiving the phase 3 dose, two patients (2.8%) experienced mild intraocular inflammation within the first 28 weeks post-dosing, which resolved. No new inflammation cases occurred with up to 3.5 years of follow-up. No 4D-150-related hypotony, endophthalmitis, vasculitis, or choroidal effusions were observed.

“The ongoing burden of frequent anti-VEGF injections for patients with wet AMD remains a significant global unmet need,” said Arshad M. Khanani, MD, MA, FASRS, Director of Clinical Research at Sierra Eye Associates. “Recent results from the PRISM study demonstrate the durable efficacy and consistent safety of a single intravitreal injection of 4D-150 in a broad wet AMD population.”

The company’s phase 3 4FRONT-1 trial has randomized over 200 patients to date, with 4FRONT-2 enrollment expected to complete in the second half of 2026.