Drug Safety Communication pertaining to the safe & effective use of Beovu® (brolucizumab) released from Novartis via a direct healthcare professional communication (DHPC) letter for the implementation of updated recommendations based on the recent safety evidence from MERLIN Study (Interventional clinical trial being conducted for the comparison of Safety and Efficacy of Brolucizumab to Aflibercept in patients with age-related macular degeneration).

Brolucizumab is a humanized monoclonal antibody indicated for the treatment of endovascular (wet) age-related macular degeneration (nAMD).

Safety concerns Identified:

Emerging safety data from the study identified adverse drug reactions – Intraocular inflammation, including retinal vasculitis and/or retinal vascular occlusion as risks following the first intravitreal injection, which were observed more during the early treatment.

Mechanism:

These reactions considered as immune-mediated events which involves development of anti-brolucizumab antibodies during treatment causing intraocular inflammation events. It was found based on the data from in vitro analysis of blood samples from patients with adverse reactions and from patients without no reported adverse reactions.

Novartis conducted two non-interventional retrospective real-world evidence studies from healthcare databases for patients with nAMD which involves treatment initiation with brolucizumab for 6-month period for identifying incidence rate of these reactions. This retrospective analysis revealed the below risk factors for the safety signals.

• Gender difference: Higher risk for intra-ocular inflammatory reactions (retinal vasculitis and/or retinal vascular occlusion) were observed more in females.
• Ethnicity: More number of incidences were observed in Japanese patients.

Important note for Healthcare professionals:

Be aware of these safety signals for brolucizumab and consider the below recommendations formulated by Novartis for implementation during clinical practice for the safe & effective usage of this medicine.

1. Close monitoring: Patients with a medical history of intraocular inflammation and/or retinal vascular occlusion in the year prior to treatment with brolucizumab are at risk of developing these intraocular inflammatory reactions and should be closely monitored.
2. Recommended dosing interval: Maintenance doses of brolucizumab (after the first 3 doses) should not be administered at intervals less than 8 weeks.
3. Risk factor consideration: Be cautious in usage of this medicine in female & Japanese population group for additional monitoring of early signs & symptoms.
4. Patient communication: Request patients to monitor/cautious for signs and symptoms of these reactions and ask them to report the same for early identification and implementation of appropriate measures for addressing the risk
5. Proactive Actions: Consider discontinuation of brolucizumab after identification of intraocular inflammatory adverse reactions and manage them promptly.

Voluntary ADR reporting:

Every medicinal product has both benefits and risks. Medicines are authorized to market based on the favorable benefit-risk profile anticipated at the time of regulatory approval/entry into market. However, the safety profile of medicine would continuously updates owing to safety data from the post marketing experience from public. If the rate of reporting of suspected adverse drug reactions (ADR) from public is line with the actual occurrence of ADRs, the time lapse for taking regulatory action can be reduced and thereby improving patient safety.

All health care professionals and consumers of pharmaceutical medicinal products are encouraged to be aware of this fact and observe/monitor for any possible adverse events, reactions, medication errors, or quality complaints of medicinal products and report the same to your respective national health authority.

This would accumulate safety evidence for medicinal products which in turn help health authorities to take regulatory actions at the earliest possibility for a better patient safety and overall public health.