Ashvattha Reports Positive DME & AMD Trial Data

Ashvattha Therapeutics has reported encouraging topline data from its Phase 2 clinical trial of migaldendranib (MGB), a potential first-in-class therapy for diabetic macular edema (DME) and wet age-related macular degeneration (nAMD), unveiled during the EURETINA Congress.

Subcutaneous VEGF Inhibitor Shows Promise in Targeting Retinal Inflammation

Migaldendranib (MGB) is an investigational vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor that is covalently linked to a hydroxyl dendrimer. This innovative design enables selective penetration of the blood-retinal barrier in inflamed tissues, allowing the drug to normalize VEGF expression in activated macrophages, microglia, and hypoxic retinal pigment epithelial cells.

Unlike conventional anti-VEGF therapies that require frequent intravitreal (IVT) injections, MGB is administered via subcutaneous (subQ) injection and is being evaluated for once-monthly, at-home administration, potentially reducing treatment burden for patients.

Study Design and Patient Population

The multicenter, chronic dosing Phase 2 study enrolled patients with prior exposure to anti-VEGF therapies. Eligible participants were confirmed to be IVT responders before beginning 40 weeks of MGB treatment in their worse-seeing study eye. Importantly, predefined criteria allowed the use of supplemental anti-VEGF IVT as needed.

Key Highlights from the Phase 2 Study

Reduced Intravitreal Injection Burden

In Study Eyes:

• Patients with DME (n=8) experienced a reduction in annualized IVT injections from 8.4 to 1.6: a 78.6% decrease.

• Patients with nAMD (n=14) saw a reduction from 8.4 to 1.4 annualized IVT injections: an 83.4% decrease.

In Fellow Eyes:

• Annualized IVT injections declined from 8.3 to 0.9, an 89.1% reduction, indicating a bilateral therapeutic benefit.

Improvements in Visual and Anatomic Outcomes

DME Study Eyes:

• +6.1 ETDRS letters gain in best-corrected visual acuity (BCVA)

• –23.3 μm reduction in central subfield thickness (CST) at Week 40

nAMD Study Eyes:

• Demonstrated similar improvements in both BCVA and CST

Favorable Safety Profile

• Subcutaneous MGB was well tolerated with no treatment-related systemic or ocular serious adverse events

• No clinically significant changes were observed in renal, hepatic, or cardiac parameters

Expert Commentary on the Study Results

Dr. Susan Schneider, Acting Chief Medical Officer at Ashvattha Therapeutics, emphasized the significance of the findings:

“These 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. With the safe systemic and ocular outcomes seen to date, MGB offers a differentiated approach that could meaningfully reduce the burden of care for patients with DME and nAMD.”

Dr. Arshad M. Khanani, MD, MA, FASRS, of Sierra Eye Associates, added:

“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. Delivering a bilateral therapeutic effect through a once-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.”