Targeting the Intravitreal Treatment Burden

Positive end-of-study outcomes in a phase 2 clinical trial appear to strongly support further development of subcutaneous migaldendranib (subQ MGB) for the treatment of diabetic macular oedema (DME) and neovascular age-related macular degeneration (nAMD).

“The top-line results show that over a 40-week duration, subQ injections of MGB in patients with active DME and nAMD were well-tolerated, associated with functional and anatomical improvements, and significantly reduced the need for supplemental intravitreal (IVT) anti-VEGF injections,” reported Arshad M Khanani MD. “Confirming a bilateral effect, fellow affected eyes had stable vision and anatomy as well as a marked reduction in need for supplemental IVT.”

Representing a new class of nanomedicine, migaldendranib is a systemic agent that covalently links a VEGF receptor tyrosine kinase inhibitor (TKI) to a hydroxyl dendrimer. It targets activated macrophages, microglia, and hypoxic retinal pigment epithelial cells, acting to shut down VEGF overexpression at the source and restore normal VEGF signalling, Dr Khanani explained.

“Migaldendranib is cleared through the kidney—avoiding liver toxicity—and [used] as a subcutaneous treatment,” he said. “It not only has the potential to treat both eyes, but is also intended to be administered at home with an autoinjector.”

The phase 2 trial investigated two regimens of MGB: 2 mg/kg every 2 weeks or every 4 weeks. Dr Khanani presented data for 8 patients with DME and 14 patients with nAMD.

Study participants needed to have demonstrated a response to prior IVT anti-VEGF treatment with recurrence of intraretinal or subretinal fluid. Potential participants underwent a 12-week run-in phase to exclude non-responders (those with no improvement in fluid at week 4) and super responders (those who had no fluid return at 12 weeks). Patients who entered the trial could receive supplemental intravitreal anti-VEGF based on predefined criteria that reflected real-world practice.

In both the DME and nAMD groups, the majority of patients (88% and 57%, respectively) had bilateral disease. When both eyes were affected, the eye with the worse BCVA was designated as the study eye.

A review of study participant safety data showed no serious ocular or systemic adverse events related to MGB nor any clinically significant changes in renal, hepatic, or cardiac values. Localised, transient injection site reactions occurred in about 8% of patients, which were mostly mild, none severe, and primarily occurred on the first injection.

“The absence of systemic safety issues is in contrast to systemic TKIs used for other indications and is consistent with MGB’s mechanism of targeting only activated cells,” Dr Khanani said.

Analyses of data from study eyes showed clinically meaningful improvements in both BCVA (+6.1 ETDRS letters) and central subfield thickness (CST; -23.3 μm) in DME eyes. Eyes with nAMD showed consistent improvement in BCVA (+4.7 ETDRS letters) and CST (-63.5 μm). Study eyes in both diagnostic groups benefited, with a marked reduction in the need for supplemental IVT anti-VEGF injections and the annualised rate decreasing from 8.4 to 1.6 injections per year. For fellow affected eyes, the annualised rate of supplemental IVT anti-VEGF injections fell from 8.3 to 0.9 injections per year.

Dr Khanani presented at EURETINA 2025 in Paris.

Arshad M Khanani MD, MA, FASRS is Managing Partner and Director of Clinical Research at Sierra Eye Associates and Clinical Professor at the University of Nevada, Reno School of Medicine, Reno, Nevada, US. arshad.khanani@gmail.com