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Novel Treatment Pathways for DME

Novel pharmacotherapies are in development for the treatment of diabetic macular edema.

We hope the combination of the current drugs as well as drugs in the pipeline … will help us to manage our patients with diabetic macular edema,” Quan Dong Nguyen, MD, said at Macula 2015.

Among promising pipeline drugs are ALG-1001, AKB-9778 and ASP-8232, he said, all targeting different pathways for treatment.

ALG-1001 is a small integrin peptide whose potency relies on anti-angiogenesis and vitreolysis to induce posterior vitreous detachment as well as vitreous liquefaction, according to Nguyen.

In a recently completed study combining ranibizumab (Lucentis) with ALG-1001 to treat choroidal neovascularization, the combined therapy reduced the area of neovascularization better than standalone therapy, he said.

A phase 2 study of ALG-1001 for treatment of DME is underway.

Another pipeline drug under study for treatment of DME, AKB-9778, is a small molecule that targets the enzyme that deactivates the Tie-2 gene. In its normal state, Tie-2 maintains the blood-retinal barrier in normal vasculature. AKB-9778 is administered via subcutaneous injection and is rapidly absorbed and rapidly eliminated.

In a phase 1 study of the molecule comparing four different doses given twice daily for 28 days, best corrected visual acuity improved by at least six letters in the three higher doses: 15 mg, 22.5 mg and 30 mg. As well, the study showed good correlation of visual acuity gain and anatomic improvement, he said.

“The Tie-2 pathway is critical in the initiation and propagation of diabetic eye disease,” Nguyen said. “AKB-9778, a small molecule activator of Tie-2, has shown promising results in early studies of diabetic eye disease.”

The TIME-2 study involving 144 patients randomized to study drug plus ranibizumab, study drug plus sham, or placebo is underway to evaluate the effect of AKB-9778 used in combination with the anti-VEGF.

A third promising molecule, ASP-8232, is a VAP-1 inhibitor that has been shown in animal models to improve the ability to reduce ocular hyperpermeability when used in combination with anti-VEGF, according to Nguyen.

Source: Healio