Future of DME resting on new mechanisms of action
When it comes to finding new treatments for diabetic macular edema (DME), there is no shortage of promising targets, said Peter A. Campochiaro, MD.
Dr. Campochiaro, director of the Retinal Cell and Molecular Laboratory and professor of ophthalmology, Wilmer Eye Institute/Johns Hopkins University, Baltimore, presented an overview of future compounds with various mechanisms of action that may change how clinicians treat DME.
Vascular endothelial growth factor (VEGF) “is going to remain an important target,” Dr. Campochiaro said, including abicipar pegol, which may have a longer duration of action than aflibercept. Single-chain, anti-VEGF antibody fragments also are being developed, and these show promise because a large amount can be injected.
“Therefore the inhibitory levels can be maintained longer in the vitreous,” he added. However, Dr. Campochiaro cautioned that these may also have a greater systemic exposure.
There are also a number of modes of sustained delivery systems being tested. For example, Genentech’s ranibizumab port delivery system (RPDS) is a refillable reservoir that may reduce treatment burden. Dr. Campochiaro said the RPDS has shown positive outcomes in an age-related macular degeneration study that could potentially be replicated in DME.
Microparticles are drugs that are incorporated into polymers and then formulated into small particles that can be injected through a syringe and needle into the eye, but then deliver drug over a sustained period of time. Graybug’s sunitinib is a tyrosine kinase inhibitor that blocks VEGFs, PDGFRs, c-MET, and DLK.
“So far, it looks like when these are injected into the vitreous, they form an aggregate that stays in the inferior vitreous base,” Dr. Campochiaro said. “Then (they) slowly erode to release this sunitinib for more than 6 months.”