Safety review committee releases report on inflammation events due to brolucizumab

The incidence of retinal vasculitis and retinal vascular occlusion after brolucizumab injections are higher than originally reported, according to a post-hoc review of the phase 3 HAWK and HARRIER trials.

This assessment—performed by an external safety review committee (SRC)—was part of Novartis’ response to the safety concerns that arose earlier this year regarding their new anti-VEGF agent. In February, the American Society of Retina Specialists (ASRS) issued a member alert regarding 14 cases of vasculitis after brolucizumab, 11 of which were designated occlusive retinal vasculitis. Although Novartis stood by the drug’s safety and efficacy, they established an external SRC in addition to launching an internal review.

Using imaging data from the HAWK and HARRIER studies, the SRC found that incidence of intraocular inflammation with brolucizumab treatment was 4.6%, which is close to what was reported in the trials (4.4%). Despite a low overall incidence (<1%) of at least moderate vision loss related to intraocular inflammation, the SRC found that the incidences of both retinal vasculitis and retinal vascular occlusion were higher than what was reported by the study investigators. Among 1,088 patients treated with brolucizumab, 23 (2.1%) had intraocular inflammation, retinal vasculitis and retinal vascular occlusion; approximately 30% of these patients had at least moderate vision loss (≥15 ETDRS letter loss) while 22% developed severe vision loss (≥30 ETDRS letter loss). Conversely, 8 (1.1%) patients in the aflibercept group had intraocular inflammation, retinal vasculitis and/or retinal vascular occlusion, with a 12.5% risk of moderate vision loss within that subgroup.

Despite disparities in the risk of vision loss associated with retinal vasculitis, the overall rate of moderate to severe vision loss remained similar between the aflibercept and brolucizumab arms: 7.4% or 81/1,088 for brolucizumab versus 7.7% or 56/729 for aflibercept.

In addition, the SRC notes that inflammatory events occurred more frequently in the first 6 months following the first dose of brolucizumab; earlier events tracked with moderate or severe vision loss.

The SRC plans to publish detailed results in a peer-reviewed publication in the upcoming months. Meanwhile, the FDA has approved a label update to include additional safety information about retinal vasculitis and retinal vascular occlusion.

Physicians should report any observed or suspected adverse events to the FDA's MedWatch Adverse Event Reporting as well as to Novartis.