4D Molecular Therapeutics has enrolled the first patients in 4SIGHT, a global phase 3 trial evaluating 4D-150, its investigational intravitreal gene therapy, in patients with diabetic macular edema (DME).
The randomized, double-masked trial will enroll 514 treatment-naïve patients and compare 4D-150 with aflibercept 2 mg (Eylea; Regeneron) administered every 8 weeks. All participants will receive 5 aflibercept loading doses, with randomization requiring demonstrated responsiveness during the run-in period.
The primary endpoint is noninferiority in mean change from baseline in best-corrected visual acuity at week 52. Secondary endpoints include treatment burden reduction and the proportion of patients achieving a 2-step or greater improvement on the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale. Supplemental aflibercept will be permitted in both groups.
4DMT also reported updated 2-year results from part 1 of the phase 1/2 SPECTRA trial. Among 9 patients receiving the phase 3 dose of 3×1010 vg/eye, mean BCVA improved by 10.8 letters and central subfield thickness decreased by 176 µm. The company reported a 61% reduction in treatment burden compared with projected every-8-week aflibercept dosing.
Among 22 SPECTRA participants, no intraocular inflammation or ocular serious adverse events were reported through 2 years.
4D-150 has received Regenerative Medicine Advanced Therapy designation from the US Food and Drug Administration (FDA) for DME. The same agent is also being evaluated in wet age-related macular degeneration in the 4FRONT program, which includes 2 phase 3 trials. RP