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Home > Safety Information > Overview

Background

Following FDA approval of Beovu for the treatment of wet AMD in October 2019, Novartis received reports of vasculitis, including retinal occlusive vasculitis. In addition, during February and March 2020, the American Society of Retinal Specialists (ASRS) shared updates with its membership regarding post-marketing case reports. Further information is available here.

Novartis initiated its own internal review of these post-marketing safety case reports including the establishment of an external Safety Review Committee (SRC) to provide an independent, objective review of these cases and a comparison with events seen in the brolucizumab Phase III trials (HAWK & HARRIER) in patients with wet AMD. Using the terminology defined by the SRC, the Novartis review of post-marketing events concluded there is a confirmed safety signal of adverse events termed as “retinal vasculitis” (RV) and/or “retinal vascular occlusion” (RO)that may result in severe vision loss. Typically, these events occurred in the presence of intraocular inflammation (IOI).

The SRC also conducted an unmasked review of a subset of imaging data from HAWK & HARRIER and indicated that they saw some of the same adverse events in the trials. They found that these events occurred on a spectrum ranging from IOI to vasculitis to occlusive events that sometimes resulted in vision loss. The findings of the SRC review of the HAWK & HARRIER trials have been published in Ophthalmology. 

Label updates have been approved by several health authorities for use in the treatment of patients with wet AMD, including the FDA and the EMA to include characterization of the adverse events, RV and RO, as part of the spectrum of IOI.

The EU summary of product characteristics (SmPC) and product information (PI) labels were updated on 28 March 2022 to include the approval for diabetic macular edema (DME) indication. 

Findings from the mechanistic study BASICHR0049

Novartis would like to inform you of the following:

  • The results from the mechanistic study analyzing blood samples from patients with wet AMD exposed to Beovu and having subsequently developed RV and/or RO, taken together with accumulated data regarding the association of treatment-emergent immunogenicity and IOI indicate a causal link between the treatment-emergent immune reaction against Beovu and the Beovu related “RV and/or RO, typically in the presence of IOI”.
  • Considering this finding, physicians should discontinue treatment with Beovu in patients who develop events of RV and/or RO.

Additional information regarding the BASICHR0049 study will be presented at an upcoming congress. We are proactively communicating this information to health authorities and will discuss potential updates to the Beovu prescribing information globally with the relevant health authorities.

Beovu continues to represent an important treatment option for patients with wet AMD, with an overall favorable benefit-risk profile.

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Results from a real-world evidence analysis

The results of a retrospective, real-world evidence analysis in wet AMD patients suggest that patients with IOI and/or occlusion in the 12 months prior to the first brolucizumab injection had the highest observed risk rate for an event of IOI and/or occlusion among patient eyes in the 6 months post-first brolucizumab treatment [Zarbin et al. Profiles and Early Outcomes of Patients Who Initiated Brolucizumab for Neovascular (Wet) Age-related Macular Degeneration (AMD) in the IRIS® Registry and Komodo Database. PO395. AAO 2020; Ip et al. The Brolucizumab Experience Thus Far: A Health Economics and Outcomes Research Analysis. AAO 2020]. Study limitations: observed rates were based on ICD codes, there was no access to patient charts, the follow-up time was 6 months with most patient eyes receiving only 1 to 2 injections and the potential overlap between IRIS® and Komodo databases is unknown. Based on such limitations of the analysis, future studies are necessary to validate these observations.