4DMT releases positive topline interim data from Part 1 of the SPECTRA clinical trial

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4D Molecular Therapeutics (4DMT) released positive topline interim data from Part 1 of the SPECTRA clinical trial. This trial is designed to evaluate 4D-150 in diabetic macular edema (DME) and alignment with the US Food and Drug Administration (FDA) on registrational pathway for 4D-150 in DME.

The data cutoff for the following results was December 13, 2024.

Objective and Design

The objective of this trial was to evaluate safety and tolerability and identify dose level for further evaluation. This was done by using stringent supplemental aflibercept criteria and enrolling patients with high central subfield thickness (CST) to maximize patient safety and assess initial clinical activity.¹

The study included 22 patients enrolled across 3 dose levels:

• 3E10 vg/eye (n=9),
• 1E10 vg/eye (n=12), and
• 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.¹

Safety and efficacy

4D-150 was well tolerated with no intraocular inflammation at any timepoint (n=21).All patients completed the 16-week topical corticosteroid taper on schedule and remained completely off steroids. No hypotony, endophthalmitis, vasculitis, choroidal effusions or retinal artery occlusions.¹

3E10 vg/eye arm:

• Sustained gain of best corrected visual acuity (BCVA) of +8.4 letters
• Sustained reduction of CST, as measured by optical coherence tomography (OCT), of -194 µm

Supplemental injections: Post-aflibercept loading doses (3), 3E10 vg/eye achieved substantially fewer supplemental injections compared to 1E10 vg/eye and projected on-label aflibercept 2mg Q8W:

• Mean injections per patient:
  • 3E10 vg/eye: 0.6, 1E10 vg/eye: 1.4, projected on-label aflibercept 2mg Q8W: 4.0
  • 3E10 vg/eye demonstrated a reduction of 61% vs. 1E10 vg/eye
  • 3E10 vg/eye demonstrated a reduction of 86% vs. projected on-label aflibercept 2mg Q8W
• 0-1 injections:
  • 8 of 9 overall (3E10 vg/eye) vs. 5 of 10 (1E10 vg/eye, 1 patient missed Week 24-32 visits)
• Injection-free:
  • 5 of 9 overall (3E10 vg/eye) vs. 2 of 10 overall (1E10 vg/eye)
  • 5 of 8 in patients treated per protocol (3E10 vg/eye)

Results to be presented in a corporate webcast on February 10, 2025. 52-week interim data update expected at a scientific conference in mid-2025¹

Next steps

The Phase 3 dose will be 3E10 vg/eye. The company also shared that FDA is aligned that a single Phase 3 clinical trial, combined with data from the 2 planned Phase 3 clinical trials in the 4FRONT wet AMD program, would be acceptable as the basis of a BLA submission for 4D-150 in DME.¹

Per FDA feedback, the Company may proceed to Phase 3 (SPECTRA Part 2 no longer needed) and is aligned with key design elements of a Phase 3 clinical trial with approximately 300-400 patients total with a primary endpoint of BCVA noninferiority vs. on-label aflibercept 2mg (5 loading doses and Q8W), and revised supplemental injection criteria (less stringent compared to Part 1 SPECTRA, in line with prior successful Phase 3 DME clinical trials).¹

Reference:

1. 4DMT Announces Positive Interim Data from 4D-150 SPECTRA Clinical Trial in DME and Alignment with FDA on Registrational Path. 4D Molecular Therapeutics, Inc. January 10, 2025. Accessed January 13, 2025. https://www.globenewswire.com/news-release/2025/01/10/3007631/0/en/4DMT-Announces-Positive-Interim-Data-from-4D-150-SPECTRA-Clinical-Trial-in-DME-and-Alignment-with-FDA-on-Registrational-Path.html