Novel Drug Delivery System for the Management of Wet AMD - Episode 4
Carl Regillo, MD and Diana Do, MD discuss the safety concerns with the use of brolucizumab in wet AMD and the impact of these concerns in their practice.
Diana Do, MD: We mentioned safety. Recently brolucizumab, which is an FDA-approved medicine, did have a safety signal associated with it. This was a new adverse event that had not been reported with other anti-VEGF agents. Brolucizumab was associated with intraocular inflammation that could lead to retinal vasculitis and retinal artery occlusion. Have you seen this in your clinical practice? What do you think of this safety signal?
Carl Regillo, MD: Fortunately, I haven’t seen this in clinical practice, but I haven’t used a lot of brolucizumab in practice. Turning the clock back, we’ve had these drugs, anti-VEGF agents—at least 1 of or 2 or so—for about 16 years in practice, circa 2006. At first it was bevacizumab and ranibizumab for many years, and then aflibercept was FDA approved and utilized. We have extensive experience over the years with all 3 drugs. All 3 show comparable efficacy and durability, averaging every 8 weeks. When you said the mean was 5 per year, you can already start to sense that we’re probably undertreating.
In the real world, we don’t get the types of vision gains maintained over time as we would like. Durability is a huge problem. And safety, though, safety wasn’t an unmet need because the safety of those 3 drugs was actually incredible. One known complication of an intravitreal injection is infection. It’s serious but rare, about 1 in 3000 or less. Occasionally, you might even get a little inflammation, sometimes more than a little, with these drugs. But look at the clinical trials: 1% or 2% at most, and none of them ever had a safety issue that you mentioned—retinal vasculitis, vascular occlusions, or vision loss from those types of problems.
Then brolucizumab came on the scene. It was FDA approved about a year and a half ago, so many of us don’t have a lot of experience with it. In the clinical trials there was an imbalance with more intraocular inflammation events— about 4% or 5% vs 1% or 2% at most with aflibercept. That’s how the comparison was in the phase 3 studies. There was an imbalance. But after the study was reanalyzed and the drug was released, we started to see these events with inflammation plus these vaso-occlusive events, which led to some vision loss.
The best we can tell right now is that the rates are 4% to 5% for IOI, intraocular inflammation. That’s not always bad. But there are vascular occlusions or retinal vasculitis 3% or so of the time and vaso-occlusive phenomenon occurring about 1% to 2% of the time—with vision loss, around 1%. It doesn’t sound like a lot, but we’ve never had those types of vision-loss problems with the other agents. Brolucizumab had a safety signal emerge right after launch. That’s why many of our colleagues and I don’t use a lot of it. It’s a last resort.
Unfortunately, it was looking promising as more durable and better drying. It was…giving us that little extra durability by maybe a couple of weeks or so. We are very excited about it, but unfortunately the safety profile is not as good as what we’re using. It’s relegated to a last resort or last line. No, I haven’t had the problem, fortunately. Then again, I haven’t used it a lot in practice. What about you? Is that your experience with brolucizumab?
Diana Do, MD: When brolucizumab was FDA approved and the clinical efficacy data were very promising, I did switch several patients over to it to try to decrease the disease activity and extend their treatment interval. I did have good success. But with the safety signal that emerged, that paused my use of it because of this risk for this potential serious adverse events with decreased vision. I relegate it to more of a last-resort medicine in patients who have very active disease despite using on-label ranibizumab or aflibercept. I haven’t seen adverse events in my patients, but if you’re still using brolucizumab, you have to monitor the patients carefully for signs of inflammation or retinal vasculitis.
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Transcript Edited for Clarity