4DMT enrolls first patient in phase 3 4FRONT-1 evaluating 4D-150 for the treatment of wet AMD

(Image Credit: AdobeStock/Khaohom Mali)

4D Molecular Therapeutics announced the first patients have been enrolled in its 4FRONT-1 phase 3 clinical trial evaluating 4D-150 for the treatment of wet age-related macular degeneration (wet AMD).

4FRONT-1 is a phase 3 multicenter, randomized, double-masked, aflibercept 2 mg comparator-controlled study of intravitreal 4D-150 in wet AMD. According to the company,¹ the primary endpoint is non-inferiority in the mean change from baseline in best corrected visual acuity (BCVA) at 52 weeks. The secondary endpoint is treatment burden reduction, comparing the number of aflibercept injections received in the 4D-150 arm versus the aflibercept comparator arm over 52 weeks. The trial will be evaluating treatment-naïve wet AMD patients at sites in North America.

David Kirn, MD, co-founder and CEO of 4DMT, commented on 4D-150 and the trial design in a press release from the company.¹

“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,” said Kirn. “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.”

In addition, the company announced its phase 3 4FRONT-2 trial for wet AMD, which has an identical design to 4FRONT-1 but will evaluate 4D-150 in both treatment-naïve and recently diagnosed, treatment-experienced wet AMD patients globally. 4FRONT-2 is expected to initiate in Q3 2025.

4D-150 is a potential backbone therapy that is designed to provide multi-year sustained delivery of anti-VEGF (aflibercept and anti-VEGF-C) from the retina with a single, safe, intravitreal injection. 4D-150 utilizes a customized and evolved intravitreal vector from 4DMT, R100, which was invented by the company through their proprietary Therapeutic Vector Evolution platform.

Arshad M. Khanani, MD, MA, FASRS, chair of the 4DMT Ophthalmology Advisory Board and a principal investigator of the 4FRONT-1 clinical trial commented on the trial in a press release from the company.¹

"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," said Khanani. "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."

Topline primary endpoint data from both 4FRONT-1 and 4FRONT-2 is expected in the second half of 2027.¹

Reference:

1. 4DMT Announces First Patients Enrolled in 4FRONT-1 Phase 3 Clinical Trial Evaluating 4D-150 in Wet AMD. Published March 10, 2025. Accessed March 10, 2025. https://ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4dmt-announces-first-patients-enrolled-4front-1-phase-3-clinical