The Australian Health Authority (TGA) approved an update of the Beovu prescribing information (PI) on June 25, 2020. The Australian PI has been updated to state that retinal vasculitis and/or retinal vascular occlusion have been reported with the use of Beovu. Concomitant intraocular inflammation was reported, but not in all cases. Prior treatment was not reported for all cases, however, some patients had previous intravitreal VEGF inhibitor therapy.
The Swiss Health Authority (Swissmedic) approved an update of the Beovu PI on June 12, 2020. The Swiss PI has been updated to state that retinal vasculitis and/or retinal vascular occlusion have been reported with the use of Beovu. In most cases intraocular inflammation was also present.
The US Food and Drug Administration (FDA) approved an update to the Beovu prescribing information on June 9, 2020. The update includes characterization of the adverse events, retinal vasculitis and retinal vascular occlusion, as part of the spectrum of intraocular inflammation noted in the original prescribing information.
The Safety Review Committee (SRC) has provided a report of their unmasked, independent analysis of brolucizumab Phase III trials (HAWK & HARRIER) adverse events. The report is available for ASRS members and can be downloaded here.
Novartis is confident that Beovu continues to represent an important treatment option for patients with wet AMD, with an overall favorable benefit/risk profile.
Novartis is fully committed to keeping the retina community informed of the latest information pertaining to the safety of Beovu.
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. Further information is available for ASRS members 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). Using the terminology defined by the SRC, the Novartis review of post-marketing events concluded there is a confirmed safety signal of rare adverse events termed as “retinal vasculitis” and/or “retinal vascular occlusion” that may result in severe vision loss. Typically, these events occurred in the presence of intraocular inflammation (IOI). For rates of adverse events in the post-marketing setting, click here.
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 intraocular inflammation to vasculitis to occlusive events that sometimes resulted in vision loss.
Adverse events as reported by study investigators were included in the Beovu US label as intraocular inflammation (4%) and retinal artery occlusion (1%). The EMA prescribing information also reports the specific type of intraocular inflammation observed and describes the occurrence of these individual events as either common or uncommon.
The update to the US label includes the addition of a sub-section dedicated to retinal vasculitis and/or retinal vascular occlusion under ‘Warnings and Precautions’ (Section 5). It also specifies that these adverse reactions are part of a spectrum of intraocular inflammation rates from the Phase III HAWK & HARRIER trials (Table 1).
To request the prescribing information for your country, click here.
Novartis believes that Beovu continues to represent an important treatment option for patients with wet AMD, with an overall favorable benefit-risk profile. The following initiatives are ongoing:
Guidance for treating physicians is provided here.
We would like to sincerely thank healthcare providers who have shared reports. You are encouraged to continue to report any observed or suspected adverse events according to local country requirements. You can also make a report to Novartis at https://www.report.novartis.com.
We will continue to provide regular updates on this website as new information becomes available.
The rates below include cases reported through June 5, 2020.*
|Adverse event†||Post-marketing adverse event rates (per 10,000 injections)‡|
|Total of three events of interest||8.65 per 10,000 injections|
1.95 per 10,000 injections
|Retinal vascular occlusion§||
2.49 per 10,000 injections
|Retinal vasculitis + retinal vascular occlusion†||
4.22 per 10,000 injections
In the HAWK & HARRIER trials, intraocular inflammation and retinal artery occlusive events were reported. Click here to access the primary manuscript published in Ophthalmology.
The efficacy and safety of Beovu was studied in two prospective, global, head-to-head, Phase III, randomized, double-masked, clinical trials HAWK (NCT02307682) and HARRIER (NCT02434328). The studies involved over 1,800 patients with wet AMD across 400 centers worldwide. The studies were designed to compare intravitreal injections of Beovu 6 mg (HAWK and HARRIER) and 3 mg (HAWK only) versus aflibercept 2 mg with the primary endpoint being change in best corrected visual acuity from baseline to Week 48, with patients followed until Week 96.
Note: Healthcare providers and clinical trial investigators report what they diagnose or observe. In a clinical trial submitted to Health Authorities, the terms reported by investigators are mapped to the closest terms found within a medical coding dictionary.
Reports from clinicians of events that have occurred during marketed use so far suggest that these events can occur as early as the first or second injection of Beovu, with patients reporting changes in vision, such as significant increase in floaters or blurry vision, within one to two weeks of treatment.
Before injecting, physicians are encouraged to look for signs of intraocular inflammation, which may include examination by slit lamp or posterior segment imaging. If active intraocular inflammation is present, you must not perform an intraocular injection and should treat the intraocular inflammation according to medical practice. Please instruct your patients to contact you immediately if they notice any changes in visual acuity or any signs of inflammation, such as eye pain, floaters, discomfort or ocular hyperemia.
As a reminder, Beovu is contraindicated in patients with ocular or periocular infections, active intraocular inflammation or known hypersensitivity to brolucizumab or any of the excipients.
Physicians, other healthcare providers and patients are encouraged to report any observed or suspected adverse events according to local country requirements. You can make a report to Novartis at https://www.report.novartis.com.