Key Takeaways
- 4DMT has completed enrollment in the global phase 3 4FRONT-2 trial evaluating investigational gene therapy 4D-150 for wet AMD, completing enrollment across both pivotal studies in the 4FRONT program
- The trial will assess noninferiority in visual acuity at 52 weeks and reduction in anti-VEGF treatment burden compared with aflibercept 2 mg administered every 8 weeks
- Topline data are expected from 4FRONT-1 in the first half of 2027 and from 4FRONT-2 in the second half of 2027, with a phase 3 diabetic macular edema trial planned to begin in the third quarter of 2026
4D Molecular Therapeutics (4DMT) has completed patient enrollment in 4FRONT-2, the second pivotal phase 3 trial evaluating its investigational gene therapy candidate 4D-150 for the treatment of wet age-related macular degeneration (AMD).
The milestone completes enrollment across both global phase 3 studies in the company's 4FRONT clinical program, with the company reporting that both trials exceeded initial enrollment projections.
"Completing global enrollment in both 4FRONT-1 and 4FRONT-2 phase 3 trials with over-enrollment and ahead of initial projections further validates 4D-150 as the potential cornerstone of a transformative, category-defining retina franchise at 4DMT," said David Kirn, MD, co-founder, president and CEO of 4DMT.
Dr. Kim added that the company expects phase 3 readouts in 2027 and plans to initiate a phase 3 study of 4D-150 in diabetic macular edema during the third quarter of 2026.
"The vision for 4D-150 is compelling because it aims to move wet AMD care beyond repeated bolus injections toward durable, continuous disease control with a single intravitreal administration as the backbone treatment," said Patricio G. Schlottmann, MD, director of the Research Department at the Charles Ophthalmic Center and ophthalmology department director at Organización Médica de Investigación in Buenos Aires, Argentina, who is also a principal investigator in the 4FRONT-2 study.
4FRONT-2 is a global, multicenter, randomized, double-masked phase 3 study comparing a single intravitreal administration of 4D-150 with aflibercept 2 mg administered every 8 weeks in patients with wet AMD. The trial enrolled both treatment-naïve patients and recently diagnosed patients with limited prior anti-VEGF treatment.
The primary endpoint is noninferiority in the mean change from baseline in best-corrected visual acuity at 52 weeks. A key secondary endpoint evaluates treatment burden by comparing the number of aflibercept injections required in the 4D-150 arm versus the comparator arm over one year. Patients in both treatment groups are eligible to receive supplemental aflibercept injections as needed.
Topline 52-week results from 4FRONT-2 are expected during the second half of 2027.
The companion trial, 4FRONT-1, is being conducted in North America with an otherwise similar study design but enrolls only treatment-naïve patients. Topline 52-week results from that study are anticipated in the first half of 2027.
