Beyond anti-VEGF: Investigative drugs, approaches abound

October 1, 2008

Drugs are under development and in clinical trials that can complement anti-vascular endothelial growth factor drugs (VEGF) and attack age-related macular degeneration in ways that differ from the anti-VEGF approach. If these prove successful, many more patients can benefit from therapy for AMD.

Hong Kong-New investigative drugs for age-related macular degeneration (AMD) may complement the anti-vascular endothelial growth factor (VEGF) agents, improve the visual results, and require fewer injections. Various routes of administration are under investigation, and combination treatments are likely to provide more favorable results, said Lawrence J. Singerman, MD, during retina subspecialty day at the World Ophthalmology Congress.

In the past two decades, much progress has been made in the treatment of AMD, especially with the introduction of anti-VEGF therapies, said Dr. Singerman, clinical professor of ophthalmology, Case Western Reserve University School of Medicine, Cleveland, and voluntary professor of clinical ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine. These drugs allow some patients to have improved vision in the presence of AMD.

"However, only about 33% to 40% of patients are able to achieve a substantial improvement in vision," he said. "There is room for improvement."

One challenge associated with anti-VEGF medications is the need for frequent administration of the drugs to "mop up" the VEGF in the eye, he added.

In contrast with currently available AMD treatments, one intravitreally administered drug, bevasiranib (Opko Health Inc.), which is under investigation for wet AMD, prevents the production of VEGF by silencing mRNA, Dr. Singerman said.

"This allows more complete elimination of VEGF," he said. "One molecule of bevasiranib eliminates thousands of VEGF proteins." A phase II study showed that the drug has an excellent safety profile, inhibits growth of choroidal neovascularization (CNV), and has the potential for longer duration of effect and fewer injections. A phase III study is evaluating bevasiranib and ranibizumab (Lucentis, Genentech).

E10030 (Ophthotech), another agent administered intravitreally, is an anti-platelet-derived growth factor drug that may induce destruction of pericytes.

"Once the pericytes are destroyed, when an anti-VEGF drug is administered, the CNV itself may be destroyed," he said. Evidence suggests that each of the previous drugs administered together with ranibizumab may be better than use of any of the drugs alone, Dr. Singerman said. He demonstrated the first three cases treated with the combination of ranibizumab and E10030 and decrease in the size of CNV.

"This is something that we did not see in the three major studies of [ranibizumab and bevacizumab]," he said. "We saw improved vision, but CNV did not decrease in size."

In all cases, the visual acuity improved, the lesion size decreased, and the findings on optical coherence tomography improved, he said.

Read the complete article in the Oct. 1, 2008 issue of Ophthalmology Times.

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