FDA to update Beovu label to include additional safety information
The FDA approved a label update for Beovu to include safety information about retinal vasculitis and retinal vascular occlusion, according to a Novartis press release.
The label update follows a Novartis announcement that it would pursue worldwide label updates to Beovu (brolucizumab-dbll). The U.S. label update, under “Warnings and Precautions,” will include a subsection about retinal vasculitis and/or retinal vascular occlusion.
The update specifies that the adverse events are “part of a spectrum of intraocular inflammation rates from the phase 3 HAWK and HARRIER trials,” according to the release.
Novartis received reports of vasculitis in 14 patients treated for wet age-related macular degeneration with Beovu since its approval by the FDA in October 2019. The company initiated an internal review of the case reports and established an external safety review committee, which confirmed a safety signal of rare adverse events termed as “retinal vasculitis” and/or “retinal vascular occlusion.”
Perspective
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As a busy retinal specialist in an academic practice, the label change was welcome and appropriate in light of these rare but devastating reported complications. Still, the decision to use brolucizumab for a patient with wet age-related macular degeneration remains a difficult one.
Every decision in medicine is a risk-benefit analysis, and when assessing risk there are three critical questions that must be answered. First, what is the statistical likelihood of a complication? For brolucizumab, the post-market data are difficult to assess without knowing the true number of administered injections, but the safety review committee (SRC) review indicated about a 2% rate of ocular inflammation with vasculitis and vascular occlusion. Second, what are the clinical implications of this complication? The SRC reported that absolute risk of greater than or equal to 15 letter vision loss in patients with inflammation was 0.7% (approximately 1/140). Third, which patients are at highest risk for this complication? Unfortunately, this remains unanswered. While the majority of patients were women, there still does not seem to be a way to either predict or pretest patients to evaluate risk of retinal vasculitis and vascular occlusion before injection. Every patient situation is unique, and clinicians will continue to broach these risk-benefit conversations with informed patients motivated to either extend anti-VEGF treatment intervals or with persistent disease activity despite ongoing anti-VEGF treatment. That being said, when patients do throw the question back at me, I personally have found it impossible to justify recommending treatment given the relatively high one in 140 risk of severe vision loss. For comparison, the risk of devastating post-injection endophthalmitis varies in studies from one in 2,500 to one in 5,000.
The retina community hopes that Novartis and our colleagues can shed more light on brolucizumab-related complications to allow us to risk stratify patients. This would make patients and clinicians more confident about utilizing the drug going forward.
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