Adverse reactions : תופעות לוואי

4.8    Undesirable effects

For wet AMD, a total of 1 088 patients treated with brolucizumab constituted the safety population in two Phase III studies. Of these, 730 patients were treated with the recommended dose of 6 mg.

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

The adverse reactions experienced following administration of Beovu in clinical studies are summarised in Table 1 below.

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 
MedDRA System organ class                                       Frequency category Immune system disorders
Hypersensitivity (including urticaria, rash, pruritus,          Common erythema)
Eye disorders
Visual acuity reduced                                           Common Retinal haemorrhage                                             Common Uveitis                                                         Common Iritis                                                          Common Vitreous detachment                                             Common Retinal tear                                                    Common Cataract                                                        Common Conjunctival haemorrhage                                        Common Vitreous floaters                                               Common BEO API OCT 24 V5_IL country specific          Page 6 of 14
Eye pain                                                       Common Intraocular pressure increase                                  Common Conjunctivitis                                                 Common Retinal pigment epithelial tear                                Common Vision blurred                                                 Common Corneal abrasion                                               Common Punctate keratitis                                             Common Blindness                                                      Uncommon Endophthalmitis                                                Uncommon Retinal detachment                                             Uncommon Conjunctival hyperaemia                                        Uncommon Lacrimation increased                                          Uncommon Abnormal sensation in eye                                      Uncommon Detachment of retinal pigment epithelium                       Uncommon Vitritis                                                       Uncommon Anterior chamber inflammation                                  Uncommon Iridocyclitis                                                  Uncommon Anterior chamber flare                                         Uncommon Corneal oedema                                                 Uncommon Vitreous haemorrhage                                           Uncommon Retinal vascular occlusion                                     Uncommon Retinal vasculitis                                             Uncommon Scleritis**                                                    Uncommon **including episcleritis

Description of selected adverse reactions

Immunogenicity
There is a potential for an immune response in patients treated with Beovu. After dosing with Beovu 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. After investigation, retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, were found to be immune-mediated adverse events related to exposure to Beovu (see section 4.4). 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. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/. and to Novartis using the following email address: safetydesk.israel@novartis.com