4D Molecular Therapeutics (4DMT) has completed enrollment in 4FRONT-2, its second pivotal phase 3 trial evaluating the investigational gene therapy 4D-150 for neovascular age-related macular degeneration (nAMD).

The global, randomized, double-masked study enrolled treatment-naïve and recently diagnosed treatment-experienced patients, with enrollment exceeding the company’s initial projections. Together with the previously completed enrollment of 4FRONT-1, the milestone completes recruitment across 4DMT's phase 3 nAMD program.

4FRONT-2 compares a single intravitreal administration of 4D-150 with aflibercept 2 mg (Eylea; Regeneron) administered every 8 weeks. The primary endpoint is noninferiority in mean change from baseline in best-corrected visual acuity at 52 weeks. A key secondary endpoint is reduction in treatment burden, measured by the number of supplemental aflibercept injections required over 52 weeks. Patients in both treatment arms are eligible to receive supplemental aflibercept as needed.

According to the company, topline 52-week results from 4FRONT-1 are expected in the first half of 2027, followed by 4FRONT-2 results in the second half of 2027.

4D-150 is an investigational adeno-associated virus (AAV)-based intravitreal gene therapy designed to provide sustained intraocular expression of aflibercept and an anti-VEGF-C biologic following a single injection. The candidate is also being developed for diabetic macular edema, with a phase 3 trial expected to begin later in 2026, according to the company.