Pagenax Adverse Reactions

A total of 1088 patients treated with Pagenax constituted the safety population in the two Phase III studies HAWK and HARRIER with a cumulative 96 weeks exposure to Pagenax and 730 patients treated with the recommended dose of 6 mg.
The most frequently reported adverse drug reactions in >5% of patients treated with Pagenax 6 mg were visual acuity reduced (7.3%), cataract (7.0%), conjunctival haemorrhage (6.3%), and vitreous floaters (5.1%).
Less common serious adverse drug reactions reported in <1% of the patients treated with Pagenax 6 mg were endophthalmitis, blindness, retinal artery occlusion and retinal detachment.
Tabulated summary of adverse drug reactions from clinical trials: Adverse drug reactions from clinical trials (Table 3) are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): 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). (See Table 3.)


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Adverse drug reactions from spontaneous reports and literature cases (frequency not known): The following adverse drug reactions have been derived from post-marketing experience with Pagenax via spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorized as not known. Adverse drug reactions are listed according to system organ classes in MedDRA. Within each system organ class, ADRs are presented in order of decreasing seriousness. (See Table 4.)


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Immunogenicity: As with all therapeutic proteins, there is a potential for an immune response in patients treated with Pagenax. The immunogenicity of Pagenax was evaluated in serum samples. The immunogenicity data reflect the percentage of patients whose test results were considered positive for antibodies to Pagenax in immunoassays. The detection of an immune response is highly dependent on the sensitivity and specificity of the assays used, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Pagenax with the incidence of antibodies to other products may be misleading.
Pre-treatment antibodies have been detected in drug-naïve subjects for a variety of biotechnology-derived therapeutic proteins including single-chain antibodies. The pre-treatment incidence of anti-brolucizumab antibodies was 35 - 52%. After dosing with Pagenax for 88 weeks, treatment-emergent anti-brolucizumab antibodies were detected in 23 - 25% of patients.
Anti-brolucizumab antibodies were not associated with an impact on clinical efficacy. Among patients with treatment-emergent antibodies, a higher number of intraocular inflammation events were observed. The clinical significance of anti-brolucizumab antibodies on safety is unclear at this time.
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.