4D Molecular Therapeutics Starts Late-Stage DME Trial As Two-Year Data Show 61% Injection Reduction
The 4SIGHT trial targets 514 patients with diabetic macular edema, backed by FDA advanced therapy designation for 4D-150.
4D Molecular Therapeutics has enrolled its first patients across multiple sites in a late-stage trial of its gene therapy 4D-150 for diabetic macular edema, the company disclosed Monday in an 8-K filing. Two-year data from an earlier mid-stage study showed patients at the planned late-stage dose needed 61% fewer injections than the standard-of-care comparison, and two of nine patients at that dose required no supplemental injections at all over the two-year period.
What The 4SIGHT Trial Looks Like
The 4SIGHT study is a global, randomized, double-masked, late-stage trial comparing 4D-150 against aflibercept 2 mg in 514 treatment-naive patients with diabetic macular edema. All patients receive five aflibercept loading doses at the outset, and both arms remain eligible for supplemental aflibercept injections throughout.
The trial's main goal — its primary endpoint — is to show 4D-150 is no worse than aflibercept at improving best corrected visual acuity at week 52. The key secondary measures are treatment burden reduction (how many fewer injections the 4D-150 arm requires versus the comparator arm through week 52) and the proportion of patients who achieve at least a two-step improvement on a standard diabetic retinopathy severity scale at week 52.
Like the company's two late-stage wet age-related macular degeneration trials in the 4FRONT program, 4SIGHT requires patients to demonstrate a response to aflibercept during the first three loading doses before randomization — a design intended to confirm that enrolled patients are genuinely responsive to anti-VEGF therapy.
4D-150 holds FDA Regenerative Medicine Advanced Therapy designation for diabetic macular edema, according to the 8-K filing. The company said it has reached alignment with both the FDA and the European Medicines Agency on a potential approval pathway that would use data from the single 4SIGHT trial combined with results from the earlier SPECTRA and PRISM mid-stage studies and the two late-stage wet AMD trials in the 4FRONT program.
Two-Year SPECTRA Data: Vision Gains And Fewer Shots
The two-year results from the SPECTRA mid-stage trial, with a data cutoff of March 12, 2026, covered 22 patients in total. Among the nine patients treated at the planned late-stage dose of 3E10 vg per eye, the mean gain in best corrected visual acuity was 10.8 letters and the mean reduction in central subfield thickness — a measure of retinal swelling — was 176 micrometers, as measured by optical coherence tomography, according to the filing.
On treatment burden, the headline figure is a 61% overall reduction: patients at the late-stage dose required a mean of 5.2 supplemental injections over two years, against a projected 13.0 injections with standard on-label aflibercept 2 mg dosing. Using the supplemental injection criteria that will apply in 4SIGHT itself — criteria the company describes as more in line with contemporary late-stage trials — the retrospective estimate rises to a 75% reduction, or a mean of 3.2 estimated supplemental injections versus the same 13.0 projected comparator figure. The company noted that actual results in 4SIGHT may differ from that retrospective estimate.
The most striking individual result: two of the nine patients at the late-stage dose remained entirely injection-free over the full two years, a 22% injection-free rate.
On safety across all 22 patients, the company reported no intraocular inflammation at any timepoint, no ocular serious adverse events, and no cases of hypotony, endophthalmitis, vasculitis, choroidal effusions, retinal artery occlusions, progression to proliferative diabetic retinopathy, or vitreous hemorrhage.
Where 4SIGHT Fits In The Broader 4D-150 Program
David Kirn, 4D Molecular Therapeutics' co-founder, president and chief executive, framed 4SIGHT as the company's second late-stage program. "Following enrollment completion of our two 4FRONT Phase 3 trials in wet AMD, 4SIGHT for DME represents our second Phase 3 program," Kirn said in a statement.
Diabetic macular edema is the second major retinal disease market the company is pursuing with 4D-150, alongside wet age-related macular degeneration. The regulatory alignment the company has described — a single late-stage trial for diabetic macular edema supported by a broader combined dataset — is a meaningful structural question for the program: if the FDA accepts that pathway, 4D-150 would need only 4SIGHT, plus the earlier mid-stage data and the wet AMD late-stage results, to support a U.S. approval application in diabetic macular edema.
FDMT shares edged up less than 1% to $13.92 in Friday trading, according to market data.
The next milestones to track are interim efficacy data from 4SIGHT as enrollment scales across its global sites, and whether the FDA formally accepts the single-trial approval pathway the company has assembled for 4D-150 in diabetic macular edema.
Sources
- 8-K Filing — 4D Molecular Therapeutics, Inc. (FDMT) — SEC EDGAR
- 4DMT Advances 4D-150 into Phase 3 for Second Large Market — globenewswire.com
