Current and Emerging Therapies for Wet Age-Related Macular Degeneration (AMD) - Episode 6

Theoretical Systemic Safety of Anti-VEGF in Wet AMD

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Panelists consider the theoretical systemic safety of anti-VEGF agents in wet AMD and discuss their role in the management of patients with risk factors.

Charles C. Wykoff, MD, PhD: Mark, you were our safety guy before, so I’ll come back to you for another safety question. We’re all aware of the injection safety risks you described. What about this theoretical systemic safety risk? You have data that you can inject anti-VEGF agents in 1 eye and see a contralateral effect? You can measure decrease in system VEGF levels with some drugs at some points in some patients. Does it play a role in your clinical management in any way? If I had to pressure test that, especially in the high-risk patients, the patient says, “I just had a stroke 2 weeks ago,” or “I just had a heart attack, the vascular path.” Are there certain populations for whom we should think about this theoretical risk?

Mark P. Breazzano, MD: It’s a great question you’re mentioning because so far, in the data we have nothing is substantiating that. There’s clearly a systemic risk from it but at the same time, there’s certainly experimental and theoretical risks. We have noticed that there are anti-VEGF levels in the bloodstream, in the plasma, that have been detected experimentally and clinically. It’s there, and it’s getting outside the eye, but is it to a clinically meaningful level? I’m not sure we know the answer, but we are more confident.

In a lot of these large major studies, we’re not finding clinical end points. They’re suggesting that we’re causing danger issues to these patients. Based on some of the quantitative data in terms of levels in the blood, ranibizumab seems to clear faster than the other drugs. Presumably because it doesn’t have that Fc component on the molecule itself. As you said, these high-risk patients, ones who had a stoke maybe, if they’re really pushing for it, there might be a conversation in which you’d try ranibizumab if they’re worried about it. Another is not necessarily in the wet AMD [age-related macular degeneration] category, but there are other indications where we might worry more about systemic bloodstream. If we had a pregnant patient with diabetic retinopathy or myopic CNV [choroidal neovascularization], that would be someone for whom we might consider ranibizumab if you had to do anti-VEGF. But I don’t think it’s super compelling to be driven that way.

Charles C. Wykoff, MD, PhD: Great comments. You guys summarized the state of play extremely well. I learned a lot. Thank you.

Transcript edited for clarity.