4DMT Announces Positive Interim Results from SPECTRA Clinical Trial for 4D-150 in Diabetic Macular Edema
4D Molecular Therapeutics (4DMT) has released promising topline interim data from Part 1 of the SPECTRA clinical trial for 4D-150, a novel treatment for diabetic macular edema (DME). The study also established alignment with the U.S. Food and Drug Administration (FDA) on the registrational pathway for 4D-150 in DME.
Objective and Study Design
The primary goal of Part 1 of the SPECTRA trial was to evaluate the safety, tolerability, and appropriate dose level of 4D-150 for further clinical evaluation.
Key Details:
• The study enrolled 22 patients with high central subfield thickness (CST) to ensure patient safety and assess initial clinical activity.
• Patients were divided across three dose levels:
• 3E10 vg/eye (n=9)
• 1E10 vg/eye (n=12)
• 5E9 vg/eye (n=1)
One patient in the 1E10 vg/eye group discontinued due to a death unrelated to 4D-150 before completing a post-baseline assessment.
Safety and Tolerability
4D-150 demonstrated a favorable safety profile:
• No intraocular inflammation observed at any timepoint (n=21).
• Patients completed the 16-week topical corticosteroid taper on schedule and remained steroid-free thereafter.
• No occurrences of:
• Hypotony
• Endophthalmitis
• Vasculitis
• Choroidal effusions
• Retinal artery occlusions
Efficacy Outcomes
3E10 vg/eye Dose Group:
• Visual Acuity:
• Sustained gain of +8.4 letters in best corrected visual acuity (BCVA).
• CST Reduction:
• -194 µm, as measured by optical coherence tomography (OCT).
Supplemental Injection Results:
Following three post-aflibercept loading doses, the 3E10 vg/eye group showed significant reductions in the need for supplemental injections:
• Mean injections per patient:
• 3E10 vg/eye: 0.6
• 1E10 vg/eye: 1.4
• Projected aflibercept 2mg Q8W: 4.0
• Injection reductions:
• 61% fewer injections vs. 1E10 vg/eye.
• 86% fewer injections vs. projected aflibercept 2mg Q8W.
Injection-Free Outcomes:
• 0-1 injections:
• 8 of 9 patients (3E10 vg/eye) vs. 5 of 10 (1E10 vg/eye).
• Injection-free patients:
• 5 of 9 (3E10 vg/eye) vs. 2 of 10 (1E10 vg/eye).
Next Steps
• The Phase 3 dose will be 3E10 vg/eye, based on the favorable safety and efficacy results.
•The FDA has approved a pathway allowing 4DMT to proceed directly to Phase 3 without the need for SPECTRA Part 2.
• The Phase 3 trial will include:
• 300-400 patients.
• Primary endpoint: BCVA noninferiority vs. aflibercept 2mg (5 loading doses, Q8W).
• Revised supplemental injection criteria aligned with prior successful Phase 3 DME trials.
Looking Ahead
A corporate webcast is scheduled for February 10, 2025, to discuss these findings further. A 52-week interim update is expected at a scientific conference in mid-2025.
The Phase 3 trial, combined with data from two planned Phase 3 trials in the 4FRONT wet AMD program, will form the basis for a Biologics License Application (BLA) submission for 4D-150 in DME.
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