Pagenax Adverse Reactions

Summary of the safety profile: Wet AMD: 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.
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%).
DME: For DME, a total of 558 patients treated with brolucizumab constituted the safety population in two Phase III studies. Of these, 368 patients were treated with the recommended dose of 6 mg.
The most frequently reported adverse reaction were cataract (9.0%), conjunctival haemorrhage (6.5%) and intraocular pressure increased (5.4%).
The most serious adverse reactions were cataract (9.0%), retinal vascular occlusion (1.1%), retinal artery occlusion (0.8%), and endophthalmitis (0.5%).
Tabulated list of adverse reactions: The adverse reactions experienced following administration of Pagenax in clinical studies are summarised in Table 3 as follows.
Adverse reactions (Table 3) 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. (See Table 3.)

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Description of selected adverse reactions: Intraocular inflammation: Based on clinical studies, intraocular inflammation related adverse events, including retinal vasculitis and retinal vascular occlusion, were reported more frequently in female patients treated with Pagenax than male patients (e.g. 5.3% females vs 3.2% males in HAWK and HARRIER).
The results of a retrospective real world evidence analysis in nAMD patients who were evaluated for up to 6 months after initiating treatment with Pagenax suggest that patients with a medical history of intraocular inflammation and/or retinal vascular occlusion in the year prior to treatment with Pagenax were more likely to present with similar events after Pagenax injection, as compared to nAMD patients with no history of these events.
Immunogenicity: There is a potential for an immune response in patients treated with Pagenax.
Wet AMD: After dosing with Pagenax for 88 weeks, treatment-emergent anti-brolucizumab antibodies were detected in 23-25% of patients.
DME: After dosing with Pagenax for 96 weeks, treatment-emergent anti-brolucizumab antibodies were detected in 16-23% of patients.
Among AMD and DME patients with treatment-emergent antibodies, a higher number of intraocular inflammation adverse reactions were observed.
Retinal vasculitis and/or retinal vascular occlusion typically in the presence of intraocular inflammation, are immune mediated adverse events related to exposure to Pagenax. This treatment emergent antibody response may develop following the first intravitreal injection (see Precautions).
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 and DME. There were no major notable differences between the groups treated with brolucizumab and comparator.