Are some patients with CNV unresponsive to anti-VEGF?

Since 2004, anti-VEGF drug injections have been shown to be highly effective in suppressing choroidal neovascularization (CNV) in the retinas of people with wet age-related macular degeneration and diabetic retinopathy. They have also been shown to suppress further CNV for as long as 12 weeks, depending upon the drug being used and the disease state of the patient. 

Some patients, however, are not responding to the therapy as expected. In spite of receiving the recommended protocol of injections every 4 weeks for at least the first 3-4 months, they are experiencing continued CNV as soon as 3 weeks after treatment. Doctors have been considering such patients “nonresponsive” and resorting to alternate or combination therapies.

But now, researchers from Harvard Medical School have come up with a contradiction to the notion that patients can be nonresponsive. They have looked at the original data from Genentech’s Lucentis (ranibizumab) study and determined that these so-called nonresponders may simply require more frequent dosing. They found this in details of Genentech’s PrONTO study, in which data on subjects with persistent CNV at 2 weeks were averaged into the data on subjects at 4 weeks.

To pursue their theory, Demetrios G. Vavvas, MD, PhD and Saghar Bagheri, MD, PhD conducted a multicenter 48 patient study. They found that optimal dosing might be shorter than 4 weeks for a sizable percentage of patients, and most patients who were considered poor or nonresponders may be seen as responding if they are evaluated prior to the standard 4-week assessment.

They concluded that these results imply that, with a current dosing regimen of 4 weeks or more, suppression of VEGF for many patients may actually exacerbate progression of CNV. Further study will be necessary to confirm this before accelerated dosing will be advised.

For a more detailed description of the study, see