4D Molecular Therapeutics Reports Positive Long-Term Phase 1/2 PRISM Data in Wet AMD

4D Molecular Therapeutics has reported promising long-term results from its Phase 1/2 PRISM clinical trial evaluating 4D-150, an investigational intravitreal gene therapy for patients with wet age-related macular degeneration (wet AMD). The therapy has shown sustained treatment benefits, including consistent visual acuity maintenance and a significant reduction in treatment burden over a follow-up period of up to two years.

Strong Results Across Patient Cohorts

In the Phase 2b recently diagnosed subgroup, which is considered most comparable to the planned Phase 3 population, patients demonstrated a 94% reduction in supplemental anti-VEGF injections through year 1 and 92% through 1.5 years, relative to projected standard dosing.

The broader Phase 2b cohort also exhibited robust outcomes, with 83% and 82% reductions in supplemental injections at the same respective timepoints.

Patients in the Phase 1/2a cohort, who had more severe and treatment-resistant disease, experienced an 83% reduction through year 1 and 79% through year 2, when compared to their injection frequency in the year prior to enrollment.

Stable Visual Acuity and OCT Control

Across all cohorts, patients maintained stable visual acuity through up to two years of follow-up. In addition, there was consistent control of central subfield thickness on optical coherence tomography (OCT), supporting the therapy’s durability and efficacy.

Favorable Dose Response and Safety Profile

The trial data showed a consistent dose response, favoring the Phase 3 dose of 3E10 vg/eye compared to a lower dose. Importantly, no cases of hypotony, endophthalmitis, vasculitis, or choroidal effusions related to 4D-150 were observed.

Among the 71 patients who received the Phase 3 dose, two patients (2.8%) experienced mild intraocular inflammation within the first 28 weeks post-dosing. These cases resolved, and no new inflammation was reported with up to 3.5 years of follow-up.

Expert Perspective

“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.”

Looking Ahead: Phase 3 Trials Underway

4D Molecular Therapeutics is continuing its clinical development with the Phase 3 4FRONT-1 trial, which has already randomized over 200 patients. Enrollment for the 4FRONT-2 trial is expected to be completed in the second half of 2026.