An internal review of post-marketing safety case reports of brolucizumab (Beovu; Novartis) has confirmed a rare occurrence of intraocular inflammation (IOI) in association with retinal vasculitis and retinal vascular occlusion.
Following FDA approval of Beovu 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, according to Novartis.
Novartis initiated its own internal review of these post-marketing safety case reports including the establishment of an external Safety Review Committee (SRC) to to provide an independent, objective review of these cases and a comparison with events seen in the brolucizumab phase 3 trials (HAWK & HARRIER). The SRC consisted of clinical trial, imaging, and uveitis experts, as well as Data Monitoring Committee members.
While the incidence of IOI observed by the SRC (4.6%) remains close to the IOI incidence reported by the investigators in the HAWK and HARRIER studies (4.4%) and the overall incidence of at least moderate vision loss due to IOI remains <1%, the SRC found that their observed incidences of both retinal vasculitis and retinal vascular occlusion were higher than the incidences reported by the investigators, according to an SRC report. The SRC classified the observations of interest as definite (28 out of a total of 50 patients with IOI or 56%) or probable (22/50 or 44%). The 2-year risk of definite or probable IOI, retinal vasculitis and/or retinal vascular occlusion for the combined brolucizumab 3mg and 6mg (HAWK) and 6mg group (HARRIER) are reported and represent a per patient risk as opposed to per injection risk:
The overall incidence of the observations of interest (i.e., IOI, retinal vasculitis and/or retinal vascular occlusion) in the aflibercept arm of the HAWK and HARRIER trials was 1.1% (8/729). The overall risk of moderate vision loss (≥15 ETDRS letters) in eyes with IOI, retinal vasculitis and/or retinal vascular occlusion in the aflibercept arms of the HAWK and HARRIER trials was <1% (1/729), with a risk of 12.5% (1/8) in the affected sub-population. A similarly careful review of these patients revealed one case of probable IOI with retinal vasculitis and retinal vascular occlusion, according to the SRC report.
Of note, despite the vision loss associated with increased incidences of IOI, retinal vasculitis and/or retinal vascular occlusion associated with brolucizumab, the overall rates of at least moderate vision loss (≥15 ETDRS letter loss) are similar between the brolucizumab and aflibercept treatment arms: 7.4% or 81/1088 in brolucizumab and 7.7% or 56/729 in aflibercept.
Novartis stated that it believes that Beovu continues to represent an important treatment option for patients with wet AMD, with an overall favorable benefit-risk profile. Novartis is updating the latest information pertaining to the safety of brolucizumab on www.brolucizumab.info.