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4D-150 for DME moving to phase 3 trial following positive interim data

Key Takeaway: 4D Molecular Therapeutics announced that its therapy 4D-150 has shown positive interim results in the SPECTRA trial for diabetic macular edema, prompting progression to a phase 3 trial. Patients receiving the highest dose experienced significant improvements in visual acuity and reduced treatment burden. The FDA has indicated that a single phase 3 trial is sufficient for biologics license application submission.
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POSITIVE FACTORS

  • 4D-150 shows promising efficacy with an 8.4 letter increase in BCVA.
  • The therapy was well tolerated with no intraocular inflammation.
  • FDA feedback supports moving directly to a phase 3 trial.

BiopharmaWatch Analysis

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+128%
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Typical move
11.2%
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Cash runway
~18 mo
Low dilution risk
Lead asset
4D-150 IVT
Phase 3 · Macular Neovascularization Secondary to Age-Related Macular Degeneration

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Key takeaways:

• Patients who received 4D-150 3E10 vg/eye experienced an 8.4 letter increase in BCVA.
• 4DMT is progressing to a phase 3 trial for 4D-150 3E10 vg/eye.
4D Molecular Therapeutics reported positive interim data from the first part of the SPECTRA clinical trial investigating 4D-150 in patients with diabetic macular edema, according to a press release.
“In the past, intravitreal approaches for sustained delivery via a genetic medicine proved challenging in DME,” Carlos Quezada-Ruiz, MD, FASRS, senior vice president, therapeutic area head, ophthalmology at 4DMT, told Healio. “Today, results from SPECTRA highlight that 4D-150 can potentially help us fulfill our mission to help as many people afflicted with DME see and live better and that intravitreal genetic medicine-enabled care is possible.”
The results include data from 21 patients enrolled at three dose levels of 4D-150 (aflibercept and anti-VEGF-C): 3E10 vg/eye, 1E10 vg/eye and 5E9 vg/eye. The therapy, delivered through a single intravitreal injection, was well tolerated with no intraocular inflammation at any time point, and all patients completed a 16-week topical corticosteroid taper and remained steroid-free, according to the release.
Through 32 weeks, patients in the 3E10 vg/eye arm gained 8.4 letters in best corrected visual acuity with a reduction in central subfield thickness of 194 µm. Patients in this arm also needed fewer supplemental injections compared with those in the 1E10 vg/eye arm.
Based on FDA feedback, 4DMT is moving to a phase 3 trial with the 3E10 vg/eye dose. Part two of SPECTRA is no longer required.
“Further, based on the review of interim data from SPECTRA and PRISM in wet [age-related macular degeneration] and the planned global 4FRONT phase 3 program for wet AMD , the FDA is aligned that a single phase 3 clinical trial is acceptable for [biologics license application] submission in DME,” Quezada-Ruiz told Healio.
4DMT expects the study to include 300 to 400 patients, and the primary endpoint will be BCVA noninferiority compared with on-label aflibercept 2 mg, according to the release.
The 32-week results suggest that 4D-150 will help retina specialists address treatment burden, a major challenge in DME, Quezada-Ruiz told Healio.
“The data from SPECTRA suggest that the sustained delivery of anti-VEGF that 4D-150 enables has the potential to address this unmet need, leading to better vision in the real world,” he said. “This also has a secondary impact on us retina specialists, reducing our environmental footprint and allowing us to serve more patients.”
At the American Society of Retina Specialists annual meeting in Long Beach, California, David Almeida, MD, MBA, PhD, presented 60-week results of SPECTRA, which demonstrated an “excellent safety profile” for 4D-150. “Through its novel R100 capsid and the natural evolution that has been directed on the 4D-150 side, we see a really safe product that can really improve the treatment burden for a lot of patients,” Almeida told Healio. Editor’s note: This article was updated on July 31, 2025, to include comments from David Almeida, MD, MBA, PhD. Reference:
Almeida D. Interim results from the SPECTRA phase 2a clinical trial evaluating intravitreal 4D-150 in adults with diabetic macular edema. Presented at: American Society of Retina Specialists annual meeting; July 30-Aug. 2, 2025; Long Beach, California.

Sources/Disclosures

Source:

Press Release
Disclosures: Quezada-Ruiz reports being senior vice president, therapeutic area head, ophthalmology at 4DMT.
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Frequently Asked Questions

What is 4D-150 used for?

4D-150 is being investigated for treating diabetic macular edema.

What were the results of the SPECTRA trial?

Patients showed an 8.4 letter increase in best corrected visual acuity.

What is the next step for 4D-150?

4D-150 is advancing to a phase 3 clinical trial based on positive interim data.

How many patients will be included in the phase 3 trial?

The phase 3 trial is expected to include 300 to 400 patients.

What is the primary endpoint of the trial?

The primary endpoint will be noninferiority in BCVA compared to aflibercept.

Last updated: Jan 14, 2025