4D Molecular Technology (4DMT) has completed patient enrollment in its first phase 3 clinical trial evaluating 4D-150, an investigational gene therapy for the treatment of wet age-related macular degeneration (AMD).
This follows the company’s previously announced plans to accelerate its phase 3 wet AMD clinical program toward a future submission for U.S. regulatory approval.
Where shall we start?
First: It helps to know about 4DMT’s Therapeutic Vector Evolution.
- What it is: A proprietary platform that uses synthetic adeno-associated virus (AAV) capsid–derived sequences to create customized vectors (such as R100, below) for advancing vector delivery–based product candidates, including 4D-150.
Then: There’s the customized R100 intravitreal (IVT) vector.
- What it does: Uses a dual transgene payload—aflibercept and a VEGF-C–inhibitory RNAi—to block four angiogenic factors driving wet AMD in order to deliver 4D-150.
How, exactly?
4D-150 is formulated to offer a multi-year, sustained, and low-dose IVT delivery of anti-VEGF from the retina.
Its clinical performance thus far:
- Check out this 52-week wet AMD data from the phase 2b PRISM trial.
- See here findings from a 60-week phase 2 analysis on its second proposed indication: diabetic macular edema (DME).
- The gene therapy has also received FDA Regenerative Medicine Advanced Therapy (RMAT) designation for DME.
Now to this phase 3 trial.
That would be the North American-based 4FRONT-1 study (NCT06864988).
This is the first registrational trial on 4D-150 in the company’s planned wet AMD phase 3 clinical program, which also includes the global 4FRONT-2 study.
What we know about it:
- The design: A multicenter, randomized, double-masked, comparator-controlled study
- The participants: An estimated 480 patients (aged 50+) diagnosed with treatment-naïve wet AMD in the study eye.
- See here for all inclusion / exclusion criteria.
- The setup: Patients randomized to receive either 4D-150 (3E10 vg/eye) or an active comparator (aflibercept 2 mg) as single-dose IVT injections over a 52-week period.
Additionally: 4DMT noted that participants in both arms will be eligible for supplemental aflibercept injections.
And what’s being measured?
The primary endpoint is non-inferiority in the mean change from baseline in best-corrected visual acuity (BCVA) at 52 weeks.
The key secondary endpoint is treatment burden reduction comparing the number of aflibercept injections received in the 4D-150 versus the aflibercept comparator arm (also over 52 weeks).
- See here for all secondary outcomes (measured over 104 weeks).
So what should we know about its enrollment?
According to 4DMT President and CEO David Kirn, MD, the study actually over-enrolled with over 500 patients expected to be randomized (surpassing that prior 480 estimate).
- Also important to note: The enrollment duration was completed ahead of investigators' initial projections—in just 11 months.
And the timeframe for a data readout?
Topline data is expected in H1 2027.
Now, what about that second phase 3 trial you mentioned?
Ah, yes: 4FRONT-2 (NCT07064759). The global study’s design is identical to 4FRONT-1, except in regard to the participants it’s enrolling:
- Both treatment-naïve and recently diagnosed treatment-experienced wet AMD patients are being recruited.
Its timeframe: Enrollment is expected to conclude in H2 2026, with topline primary endpoint data to follow in H2 2027.
Duly noted. And lastly, refresh me on the end-game goal.
The accelerated timelines for both 4FRONT-1 and 4FRONT-2 support 4DMT’s intent to submit a Biologics License Application (BLA) for 4D-150’s wet AMD indication in the near future.
Of course, this is all dependent on the studies’ success in meeting their outcome measures …
As always, stay tuned for updates!