4DMT completes 4FRONT-2 Phase 3 enrolment four months ahead of schedule
4D Molecular Therapeutics (Nasdaq: FDMT) has completed enrolment for 4FRONT-2, its second global Phase 3 clinical trial evaluating 4D-150 in wet age-related macular degeneration (wet AMD). The Emeryville, California-based company said enrolment concluded roughly four months ahead of original projections and that the trial exceeded its planned size, with the final patient count expected to surpass 500 participants. Final patient randomisation is anticipated in the third quarter of 2026.
The milestone follows the earlier completion of 4FRONT-1, the North American arm of the Phase 3 programme focused on treatment-naïve patients. The two trials share an identical design: a multicenter, randomised, double-masked study comparing intravitreal 4D-150 against aflibercept 2 mg administered every eight weeks. The primary endpoint in both trials is non-inferiority in mean change from baseline in best-corrected visual acuity at 52 weeks, with a key secondary endpoint measuring reduction in the total number of aflibercept injections required over the same period. 4FRONT-1 topline data is expected in the first half of 2027; 4FRONT-2 results are expected in the second half of that year.
What 4D-150 is designed to do
4D-150 is a gene therapy candidate engineered to deliver sustained, multi-year expression of two anti-VEGF proteins, aflibercept and anti-VEGF-C, within the retina following a single intravitreal injection. It uses 4DMT's proprietary R100 AAV vector, developed through the company's Therapeutic Vector Evolution platform. The central commercial proposition is that durable, continuous anti-VEGF coverage from one injection could replace the frequent repeat bolus injections that currently define standard of care in wet AMD, a burden that investigators and patient advocates have long cited as a driver of undertreatment and preventable vision loss.
Julie Clark, chief medical officer of 4DMT, said the enrolment completion brings the company "one step closer to confirming the clinical evidence that 4D-150 can meaningfully reduce treatment burden while preserving vision outcomes." Patricio G. Schlottmann, a principal investigator in 4FRONT-2 and director of the research department at the Charles Ophthalmic Center in Buenos Aires, said the vision for 4D-150 is "compelling because it aims to move wet AMD care beyond repeated bolus injections toward durable, continuous disease control."
Competitive landscape and what comes next
Wet AMD is one of the largest addressable markets in ophthalmology. More than four million individuals are expected to be affected across the US, EU and Japan in the next five years, with an estimated 200,000 new diagnoses each year in the US alone. The current standard of care centres on approved anti-VEGF agents including aflibercept, ranibizumab and faricimab, all administered by repeat intravitreal injection. The market for durable or reduced-frequency alternatives has attracted substantial attention: Adverum Biotechnologies, Regenxbio and Gyroscope Therapeutics (now part of Novartis) have all pursued gene therapy approaches in wet AMD with varying degrees of clinical success, making the 4FRONT readouts among the most closely watched data events in the retinal gene therapy field over the coming 18 months.
Beyond wet AMD, 4DMT said it plans to initiate a Phase 3 trial of 4D-150 in diabetic macular edema in the third quarter of 2026, extending the potential commercial footprint of the programme into a second large retinal vascular indication. The company's pipeline also includes 4D-710, a genetic medicine for cystic fibrosis delivered by aerosol, though wet AMD remains the near-term value driver.
Investors will be focused on whether the 52-week BCVA non-inferiority bar is cleared in both trials while meaningful injection burden reduction is demonstrated in the treatment arm. A clean package across both endpoints would substantially strengthen 4DMT's regulatory and commercial position ahead of a potential BLA submission.