New drugs in the pipeline target novel pathways for treatment of diabetic retinopathy

from NEI

There is exciting on-going research in the field of treatments for patients with diabetic macular edema (DME). There is a long list of drugs in the pipeline for treating this disease that affects a significant number of people around the world. Pipeline drugs target novel pathways to treat diabetic eye disease.



Among promising pipeline drugs are ALG-1001, AKB-9778 and ASP-8232 that target different pathways for treatment of diabetic retinopathy.

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ALG-1001 (Allegro Ophthalmics) is a small integrin peptide whose potency relies on anti-angiogenesis and vitreolysis to induce posterior vitreous detachment as well as vitreous liquefaction. As shown in clinical studies to date, it has demonstrated regression and inhibition of new blood vessel formation, as well as reduction in vascular leakage to maintain and restore vision, while significantly reducing the current burden of intravitreal injections. In a recent study combining Lucentis (ranibizumab) with ALG-1001 to treat choroidal neovascularization, the combined therapy reduced the area of neovascularization better than standalone therapy. A phase 2 study of ALG-1001 for treatment of DME is currently ongoing.

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Another pipeline drug under study for treatment of DME, AKB-9778 (Aerpio Therapeutics), is a small molecule that targets the enzyme that deactivates the Tie-2 gene, which effectively blocks vascular leak and new blood vessel formation (angiogenesis). Tie2 signaling is responsible for stabilizing blood vessels and maintaining vascular integrity. Levels of circulating Ang2 dramatically increase in a number of disease states involving vascular leak and pathologic angiogenesis. By binding to the Tie2 receptor, Ang2 inhibits Tie2 signaling which in turn compromises vascular integrity and promotes vascular leak and pathologic angiogenesis. The HPTPß enzyme, which is the target of AKB-9778, acts as a negative regulator, or brake, at the Tie2 receptor. AKB-9778 works by inhibiting HPTPß and effectively removes this negative regulation on the Tie2 receptor. This action restores Tie2 signaling and overcomes the effects of the Angiopoietin-2.

AKB-9778 is injected subcutaneously and has rapid absorption and elimination characteristics. In a phase 1 study of the drug that compared four different doses given twice a day for 28 days, visual acuity improved by at least six letters when the dose was a bit higher - 15 mg, 22.5 mg and 30 mg. The study results also showed good correlation between visual acuity improvement and anatomic improvement. The currently on-going TIME-2 study involves 144 patients who are randomized to the study drug plus lucentis, study drug plus a sham, or placebo will possibly be able to evaluate the effect of AKB-9778 used in combination with the anti-VEGF.

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Another promising molecule is the ASP-8232 (Astellas Pharma), which 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.

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