DME treatment advancements on horizon

Chicago-There has been considerable progress in treatment for diabetic macular edema (DME) in the last several years, but a look at the investigational pipeline indicates further advances are likely on the horizon, said Peter A. Campochiaro, MD.

“VEGF antagonists are now the foundation of treatment for DME, and they are here to stay,” said Dr. Campochiaro, George S. & Dolores Doré Eccles Professor of Ophthalmology and Neuroscience, Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD. “However, there are unmet medical needs as many patients have residual edema despite monthly injections, which suggests a contributory role of factors other than VEGF.

More in this issue: Role of anti-VEGF for cornea, ocular surface disease still emerging

“In addition, many patients who respond completely require frequent injections, which is a burden,” he continued.

In his review of what is new and coming in DME treatment, Dr. Campochiaro said there is potential for improvement in anti-VEGF therapy using agents with greater durability, and an investigational anti-VEGF DARPin (abicipar pegol, Allergan) looks promising in that regard. Furthermore, there may be systems for sustained delivery or gene transfer of VEGF binding proteins in the future.

Dr. Campochiaro noted that two corticosteroid intravitreal implants were recently approved in the United States for treatment of DME (Ozurdex, Allergan; Iluvien, Alimera Sciences). They offer a second-line option for some patients, especially for individuals not susceptible to steroid-induced IOP elevation, who represented about 60% of the population in clinical trials.

In addition, there are investigational agents targeting alternative pathways that are showing promising results in early clinical studies. These include AKP9778 (Aerpio Therapeutics), a Tie2 activator, and ALG-1001 (Luminate, Allegro Ophthalmics), an antipermeability peptide with an RGD sequence that targets several integrin receptors.

AKB-9778 is a small molecule inhibitor of vascular endothelial-protein tyrosine phosphatase. In a phase Ib/IIa dose-escalation study investigating four different doses administered by subcutaneous injection twice daily for 28 days, there was some heterogeneity in response.

However, many patients achieved substantial reduction from very severe edema, and in the three highest dose groups, visual acuity improved in the majority of patients and by a mean of about 6 letters.

ALG-1001was studied in a phase I trial where 15 patients were treated with a 2-mg dose monthly for 3 months and then followed for 3 months. Eight of 15 subjects achieved a best-corrected visual acuity (BCVA) improvement ≥15 letters, BCVA improved by a mean of 11 letters, and some patients had a substantial reduction in foveal thickness that was maintained for 3 months after the last injection.