First Patients Enrolled in 4FRONT-1 Phase 3 Trial for Wet AMD Treatment

On March 10, 2025, 4D Molecular Therapeutics (4DMT), a prominent biotechnology company based in Emeryville, California, announced the enrollment of initial patients in its 4FRONT-1 Phase 3 clinical trial. This trial is designed to evaluate the efficacy of 4D-150 in treating wet age-related macular degeneration (wet AMD). The undertaking of this trial signifies a pivotal moment for 4DMT as it transitions into a Phase 3 company.

David Kirn, M.D., the co-founder and CEO of 4DMT, expressed optimism about the potential impact of 4D-150, highlighting its ability to meet the critical needs of millions of patients suffering from wet AMD and diabetic macular edema (DME). These patients currently endure the inconvenience of frequent eye injections to maintain their vision. Dr. Kirn emphasized that the trial's design, the therapeutic capacity of 4D-150, and the promising data gathered thus far suggest a path toward successful product approval and eventual market introduction. He envisages 4D-150 becoming a fundamental, long-lasting treatment option seamlessly integrated into the practices of retina specialists.

The 4FRONT-1 trial is a multicenter, randomized, double-masked study comparing intravitreal 4D-150 to a standard aflibercept 2 mg (Q8W) regimen in patients with wet AMD. The primary objective is to demonstrate non-inferiority in improving best-corrected visual acuity (BCVA) over 52 weeks. A significant secondary aspect is the reduction in treatment frequency, comparing the number of aflibercept injections in the 4D-150 group versus the control group within the same period. Participants in both study groups can receive additional aflibercept injections if needed. The trial is underway at various North American locations with treatment-naïve wet AMD patients.

In addition to 4FRONT-1, a second Phase 3 trial named 4FRONT-2 is planned. This trial will extend the evaluation of 4D-150 to a global patient population, including both newly diagnosed and previously treated wet AMD patients. The commencement of 4FRONT-2 is anticipated in the third quarter of 2025, with primary endpoint data from both trials expected in late 2027.

Dr. Fuad Makkouk, a principal investigator of the 4FRONT-1 trial, acknowledged the burden that wet AMD places on patients, their families, and caregivers due to the need for frequent eye injections. He noted that the early data suggests that 4D-150 could significantly enhance patient experience by reducing treatment frequency and improving quality of life.

Another principal investigator, Dr. Arshad M. Khanani, who also chairs the 4DMT Ophthalmology Advisory Board, shared insights from his involvement in the earlier PRISM Phase 1/2 study of 4D-150. He pointed out the drug's promising potential to change the progression of wet AMD and lessen the treatment load. Dr. Khanani expressed enthusiasm about the 4FRONT-1 trial and the opportunity to work with 4DMT and other researchers to potentially offer 4D-150 to patients, thereby providing a substantial improvement in managing their condition.

4D-150 is positioned as a pioneering therapy aimed at offering sustained multi-year anti-VEGF treatment through a single intravitreal injection. Using a specialized intravitreal vector, R100, developed through 4DMT's Therapeutic Vector Evolution platform, 4D-150 targets wet AMD and diabetic macular edema, aiming to minimize the necessity for frequent injections while maintaining vision.

Wet AMD is a widespread condition with over four million people projected to be impacted in major markets such as the U.S., EU, and Japan in the upcoming years. It involves abnormal blood vessel growth in the retina, leading to visual impairment and potentially blindness without treatment.

4DMT continues to advance its innovative therapies, with 4D-150 as its leading product candidate in the fight against retinal vascular diseases, and 4D-710 as a genetic medicine showing promise for cystic fibrosis treatment. 4DMT's product candidates are currently undergoing clinical or preclinical trials, pending approval by relevant regulatory authorities.