Brolucizumab

No reproductive or fertility studies have been conducted. VEGF inhibition has been shown to affect follicular development, corpus luteum function and fertility. Based on the mechanism of action of VEGF inhibitiors, there is a potential risk for female reproduction, and to embryofoetal development.

Transient increases in intraocular pressure have been seen within 30 minutes of intravitreal injection with vascular endothelial growth factor (VEGF) inhibitors, including brolucizumab. Special precaution is needed in patients with poorly controlled glaucoma (do not inject brolucizumab while the intraocular pressure is ≥30 mmHg). Both intraocular pressure and perfusion of the optic nerve head must be monitored and managed appropriately.

Treatment should be discontinued in subjects with rhegmatogenous retinal detachment or stage 3 or 4 macular holes.

There are no or limited amount of data from the use of brolucizumab in pregnant women. Animal studies are insufficient with respect to reproductive toxicity. Although the systemic exposure after ocular administration is very low, brolucizumab should not be used during pregnancy unless the potential benefit outweighs the potential risk to the foetus.

It is unknown whether brolucizumab is excreted in human milk. A risk to the breast-fed newborn/infant cannot be excluded. Brolucizumab is not recommended during breast-feeding and breast-feeding should not be started for at least one month after the last dose when stopping treatment with brolucizumab. A decision must be made whether to discontinue breast-feeding or to abstain from brolucizumab therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Women of childbearing potential

Women of childbearing potential should use effective contraception during treatment with brolucizumab and for at least one month after the last dose when stopping treatment.with brolucizumab.

Fertility

No reproductive or fertility studies have been conducted. VEGF inhibition has been shown to affect follicular development, corpus luteum function and fertility. Based on the mechanism of action of VEGF inhibitiors, there is a potential risk for female reproduction, and to embryofoetal development.

Brolucizumab has a minor influence on the ability to drive and use machines due to possible temporary visual disturbances following the intravitreal injection and the associated eye examination. Patients should not drive or use machines until visual function has recovered sufficiently.

Summary of the safety profile

The most frequently reported adverse reactions were reduced visual acuity (7.3%), cataract (7.0%), conjunctival haemorrhage (6.3%) and vitreous floaters (5.1%). The most serious adverse reactions were blindness (0.8%), endophthalmitis (0.7%), retinal artery occlusion (0.8%) and retinal detachment (0.7%).

Tabulated list of adverse reactions

Adverse reactions (Table 1) are listed according to the MedDRA system organ class. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first. Frequency categories for each adverse reaction are based on the following convention: very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1. Frequencies of adverse reactions in clinical studies and post-marketing experience:

Description of selected adverse reactions

Immunogenicity

There is a potential for an immune response in patients treated with brolucizumab. After dosing with brolucizumab for 88 weeks, treatment-emergent anti-brolucizumab antibodies were detected in 23-25% of patients. Among patients with treatment-emergent antibodies, a higher number of intraocular inflammation adverse reactions were observed. The clinical significance of anti-brolucizumab antibodies on safety is unclear at this time. Anti-brolucizumab antibodies were not associated with an impact on clinical efficacy.

Product-class-related adverse reactions

There is a theoretical risk of arterial thromboembolic events, including stroke and myocardial infarction, following intravitreal use of VEGF inhibitors. A low incidence rate of arterial thromboembolic events was observed in the brolucizumab clinical studies in patients with AMD. There were no major notable differences between the groups treated with brolucizumab and comparator.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.