4DMT Enrolls First Patients in Phase 3 Clinical Trial of 4D-150 for Wet AMD

4D Molecular Therapeutics (4DMT) has officially commenced its Phase 3 clinical program for 4D-150, enrolling the first patients in the 4FRONT-1 trial across multiple sites. This marks a major milestone in the development of a potential long-term treatment for wet age-related macular degeneration (AMD).

A Milestone Moment for 4DMT

David Kirn, MD, Co-founder and CEO of 4DMT, emphasized the significance of this milestone in a company press release:

“This is a historic moment for 4DMT as we become a Phase 3 company following our initiation of the 4FRONT-1 clinical trial. 4D-150 has the clear potential to address the greatest unmet needs for the millions of patients with wet AMD and DME: multi-year relief from frequent and burdensome injections into the eye and preservation of their eyesight. We believe the design of the 4FRONT Phase 3 trials, the design of 4D-150 itself, and the compelling clinical data generated to date position us for a successful product approval and commercialization. As a result of our innovation, 4D-150 has the potential to become the established durable backbone therapy for these diseases and to fit seamlessly into clinical practice and economic models for retina physicians.”

Overview of the 4FRONT-1 Phase 3 Trial

The 4FRONT-1 trial is a multicenter, randomized, double-masked study evaluating intravitreal 4D-150 in treatment-naïve wet AMD patients across North America. Key aspects of the trial include:

       • Comparator: Aflibercept 2 mg (Q8W) as the control treatment.

       • Primary Endpoint: Noninferiority in best corrected visual acuity (BCVA) change from baseline at 52 weeks.

       • Key Secondary Endpoint: Reduction in treatment burden, assessed by the number of aflibercept injections required in the 4D-150 arm versus the aflibercept comparator arm over 52 weeks.

       • Supplemental Injections: Patients in both arms will be eligible for additional aflibercept injections as needed.

4FRONT-2: Expanding the Phase 3 Program

In addition to 4FRONT-1, 4DMT plans to initiate 4FRONT-2 in Q3 2025, a second Phase 3 trial with an identical study design but including both treatment-naïve and recently diagnosed, treatment-experienced wet AMD patients globally. Topline primary endpoint data from both trials is anticipated in the second half of 2027.

Expert Insights on 4D-150’s Potential

Arshad M. Khanani, MD, MA, FASRS, Chair of the 4DMT Ophthalmology Advisory Board and principal investigator for 4FRONT-1, expressed optimism about the trial and the potential impact of 4D-150:

“As an investigator in the PRISM Phase 1/2 study with 4D-150, I’ve had the opportunity to see firsthand its potential to alter the course of the disease and reduce the treatment burden for patients with wet AMD. I’m thrilled to participate in the 4FRONT-1 trial and look forward to collaborating with the dedicated team at 4DMT and my fellow investigators to potentially bring 4D-150 to patients with wet AMD, with the chance to make a lasting difference in their lives.”

About 4D-150: A Potential Game-Changer in Retinal Therapy

4D-150 is designed as a single intravitreal injection gene therapy to provide multi-year sustained anti-VEGF therapy for wet AMD and diabetic macular edema (DME). Key features include:

       • Sustained delivery of aflibercept and anti-VEGF-C from the retina.

       • Utilizes 4DMT’s proprietary intravitreal vector, R100, developed through the company’s Therapeutic Vector Evolution platform.

By significantly reducing the frequency of injections, 4D-150 has the potential to improve patient adherence, enhance outcomes, and redefine the standard of care for wet AMD and DME.

Conclusion

The initiation of 4FRONT-1 marks a major step forward in the clinical development of 4D-150, with hopes of bringing a long-term, effective solution to millions of wet AMD patients. With topline data expected in 2027, 4DMT’s innovative gene therapy approach could pave the way for a new era in durable retinal disease treatment.