4DMT Announces Positive Interim Data from 4D-150 SPECTRA Clinical Trial in DME

4D Molecular Therapeutics announced topline interim data from Part 1 of its SPECTRA clinical trial evaluating 4D-150 for the treatment of diabetic macular edema (DME). The company said it has achieved alignment with the FDA on the registrational pathway for 4D-150 in DME, advancing its phase 3 development plans.

The SPECTRA clinical trial, designed to assess the safety, tolerability, and dose optimization of 4D-150, enrolled 22 patients across three dose levels: 3E10 vg/eye, 1E10 vg/eye, and 5E9 vg/eye. Interim data, with a cutoff date of December 13, 2024, revealed that 4D-150 demonstrated encouraging safety and efficacy profiles.

Safety Findings (n=21)

• 4D-150 was well tolerated, with no cases of intraocular inflammation, hypotony, endophthalmitis, vasculitis, choroidal effusions, or retinal artery occlusions
• All patients completed a 16-week topical corticosteroid taper and remained off steroids throughout the study

Efficacy Results Through 32 Weeks (3E10 vg/eye Dose Level)

• Patients in the 3E10 vg/eye group experienced a sustained +8.4 letter gain in best corrected visual acuity (BCVA) and a -194 µm reduction in central subfield thickness (CST) on optical coherence tomography (OCT)
• Mean supplemental injections for 3E10 vg/eye patients were significantly lower (0.6 injections per patient) compared to 1E10 vg/eye (1.4 injections) and the projected frequency for aflibercept 2mg Q8W (4.0 injections)
• The 3E10 vg/eye dose level achieved an 86% reduction in injections versus on-label aflibercept Q8W and a 61% reduction versus the 1E10 vg/eye dose group

“The promising initial safety and clinical activity data of 4D-150 in DME patients, together with its success in wet AMD, reinforce its potential across multiple VEGF-driven retinal diseases,” Carlos Quezada-Ruiz, MD, FASRS, Senior Vice President and Therapeutic Area Head of Ophthalmology at 4DMT, said in a company news release. “4D-150 could represent a transformative therapy, offering multi-year sustained VEGF inhibition with a single intravitreal injection, addressing the real-world challenges of frequent bolus injections and improving disease management.”

Based on the SPECTRA and PRISM trial data, the FDA has agreed that a single phase 3 clinical trial for 4D-150 in DME will be sufficient for a Biologics License Application (BLA) submission. Key Phase 3 trial design elements include:

• Approximately 300-400 patients enrolled
• A primary endpoint of BCVA noninferiority compared to on-label aflibercept (2mg with five loading doses followed by Q8W dosing)
• Revised supplemental injection criteria aligned with previous successful DME Phase 3 trials

“Simplifying the development pathway with a single phase 3 trial represents a major step forward for 4D-150 as a pipeline-in-a-product,” said David Kirn, MD, Co-founder and CEO of 4DMT. “With strong FDA support and the differentiated clinical profile of 4D-150, we are poised to bring a transformative therapy to DME patients in the near future.”