Ashvattha reports positive phase 2 results for migaldendranib in DME and nAMD

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Ashvattha Therapeutics shared positive topline data from its phase 2 study of migaldendranib (MGB) for the treatment of diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD). The topline end-of-study results were announced at the 25^th European Society of Retina Specialists (EURETINA) Annual Congress held September 4-7 in Paris.¹

The 40-week phase 2 clinical trial was a multicenter, chronic dosing trial for the evaluation of the safety and efficacy of subcutaneous MGB, “an investigational VEGF receptor tyrosine kinase inhibitor covalently linked to a hydroxyl dendrimer, designed to shut down VEGF expression in activated macrophages and microglia, and hypoxic retinal pigment epithelial cells,” a press release said.¹

Enrolled participants were previously anti-VEGF-treated DME and nAMD patients. Additionally, responders to intravitreal (IVT) anti-VEGF were identified before the 40-week MGB treatment period, and the criteria for supplemental anti-VEGF IVT while receiving subQ MGB during the study were pre-defined.¹ The enrolled participants’ worse-seeing eye was designated as the study eye.

“Over the 40-week duration of this trial, MGB was well tolerated, and we observed improvements in both vision and retinal anatomy, along with a significant reduction in the need for supplemental intravitreal injections in patients with active nAMD and DME,” Arshad M. Khanani, MD, MA, FASRS, Managing Partner and Director of Clinical Research at Sierra Eye Associates, said in a press release.

“Delivering a bilateral therapeutic effect through a one-monthly subcutaneous injection represents a meaningful advancement for patients with these vision-threatening retinal diseases, with the potential to enhance real-world outcomes and overall quality of life.”

Key findings of the 40-week phase 2 clinical trial include:¹

• The annualized rate of IVT injections in all study eyes (DME and nAMD) decreased from 8.4 to 1.6 per year, or a 78.6% (4.7-fold) DME (n=8) and an 83.4% (6-fold) nAMD (n=14) reduction in the need for supplemental anti-VEGF versus pre-study IVT.
• A bilateral MGB treatment benefit was demonstrated with the annualized rate of IVT injections in all fellow eyes, decreasing from 8.3 to 0.6 per year, or an 89.1% (9.1-fold) reduction in the need for supplemental anti-VEGF versus pre-study IVT.
• The mean change from baseline out to week 40 was +6.1 ETDRS letters in best corrected visual acuity (BCVA) and -23.3 μm in central subfield thickness (CST) in DME study eyes.
• Improvements in BCVA and CST were also observed in nAMD study eyes.
• SubQ MGB is safe and well tolerated, with no treatment-related systemic or ocular serious adverse events reported and no clinically significant changes from baseline in renal, hepatic, or cardiac values.

“The phase 2 results demonstrate the potential of MGB to address one of the biggest challenges in retinal care today—the treatment burden associated with frequent in-office intravitreal injections,” Susan Schneider, MD, Acting Chief Medical Officer of Ashvattha Therapeutics, said in a press release.

Current anti-VEGF therapies require repeated IVT injections directly into each affected eye. On the contrary, MGB is subcutaneously delivered, providing a differentiated mechanism of action by crossing the blood-retinal barrier in regions of inflammation and selectively normalizing VEGF expression in activated macrophages and microglia and hypoxic retinal pigment epithelial cells.

MGB reduces the need for anti-VEGF IVT injections by reducing VEGF expression, rather than blocking VEGF signaling.

“With the safe systemic and ocular outcomes seen to date, MGB offers a differentiated approach that has the possibility to enable monthly at-home subcutaneous administration and could meaningfully reduce the burden of care for patients with DME and nAMD, conditions that are chronic and typically bilateral,” Schneider said.

Reference:

1. Morningstar I. Ashvattha Therapeutics Announces Positive Topline 40-Week Phase 2 Results for Migaldendranib in Diabetic Macular Edema and Neovascular Age-Related Macular Degeneration. Morningstar, Inc. Published September 4, 2025. Accessed September 4, 2025. https://www.morningstar.com/news/globe-newswire/9523134/ashvattha-therapeutics-announces-positive-topline-40-week-phase-2-results-for-migaldendranib-in-diabetic-macular-edema-and-neovascular-age-related-macular-degeneration