Clinical Studies:
SPECTRA
Citation: 4D Molecular Therapeutics. SPECTRA: Interim Results from the Phase 1 Study of 4D-150 for Wet AMD [PowerPoint presentation]. 4D Molecular Therapeutics; May 2024. Accessed May 13, 2025. Link
Key Points
- SPECTRA presented interim Phase 1 clinical trial data assessing the safety, tolerability, and optimal dose of 4D-150, an intravitreal gene therapy.
- 22 patients were enrolled across three dose levels: 3E10 vg/eye (n=9), 1E10 vg/eye (n=12), and 5E9 vg/eye (n=1).
- In the 3E10 vg/eye arm, treatment with 4D-150 resulted in a sustained improvement in best corrected visual acuity (BCVA) of +8.4 letters and a sustained reduction in central subfield thickness (CST) of –194 μm.
- No intraocular inflammation was observed at any dose level or timepoint. All patients completed the 16-week topical steroid taper as scheduled and remained off steroids thereafter. There were no cases of hypotony, endophthalmitis, vasculitis, choroidal effusions, or retinal artery occlusion.
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Objective
The trial aimed to evaluate the safety and tolerability of 4D-150 and identify an appropriate dose level for further evaluation.
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Study Design
Part I analysis at 32 weeks of a prospective, multicenter, randomized trial.
Study Subjects
- 22 patients enrolled across 3 dose levels: 3E10 vg/eye (n=9), 1E10 vg/eye (n=12), 5E9 vg/eye (n=1).
- 1 patient in 1E10 vg/eye arm terminated the study due to death unrelated to 4D-150, prior to completion of a post-baseline assessment.
- To maximize patient safety and assess initial clinical activity, the study applied stringent supplemental aflibercept criteria and enrolled patients with elevated central subfield thickness (CST).
Results (32 weeks)
- Efficacy at 32 weeks:
- Treatment with 4D-150 led to a sustained improvement in BCVA of +8.4 letters and a sustained reduction in CST of –194 μm, as measured by OCT.
- Supplemental Injections:
- Following the initial three aflibercept loading doses, patients in the 3E10 vg/eye arm required substantially fewer supplemental injections compared to those in the 1E10 vg/eye arm and the projected number for on-label aflibercept 2 mg every 8 weeks (Q8W).
- The mean number of supplemental injections per patient was 0.6 in the 3E10 vg/eye group, compared to 1.4 in the 1E10 vg/eye group and 4.0 projected for aflibercept 2 mg Q8W—representing a 61% reduction versus 1E10 and an 86% reduction versus projected aflibercept.
- Injection-free outcomes further support efficacy: 8 of 9 patients in the 3E10 group received 0–1 injections (vs. 5 of 10 in 1E10), and 5 of 9 patients in the 3E10 group remained completely injection-free, including 5 of 8 patients treated per protocol.
Conclusions
- 4D-150 continues to be well tolerated.
- Based on its review of interim data from the SPECTRA and PRISM studies, along with the planned global Phase 3 program for wet AMD, the FDA confirmed that a single Phase 3 clinical trial would be acceptable to support a Biologics License Application (BLA) submission in diabetic macular edema (DME). Per FDA feedback, the company may proceed directly to Phase 3, and SPECTRA Part 2 is no longer required.
- 52-week interim data update expected at a scientific conference in mid-2025.