Vsiqq Adverse Reactions

Wet AMD population: A total of 1,088 patients treated with brolucizumab constituted the safety population in the two Phase III studies (HAWK and HARRIER) with a cumulative 96 weeks exposure to Brolucizumab (Vsiqq) and 730 patients treated with the recommended dose of 6 mg.
The most frequently reported adverse drug reactions in >5% of patients treated with Brolucizumab (Vsiqq) 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 Brolucizumab (Vsiqq) 6 mg were endophthalmitis, blindness, retinal artery occlusion and retinal detachment.
DME population: The safety of Brolucizumab (Vsiqq) was studied in two, Phase III active controlled studies (KESTREL and KITE) conducted respectively in 368 patients with visual impairment due to DME treated with the recommended dose of brolucizumab 6 mg for 52 weeks.
The ocular and non-ocular events in the KESTREL and KITE studies were reported with a frequency and severity similar to those seen in the wet AMD trials. Retinal vascular occlusion was reported in two patients (0.5%) treated with Brolucizumab (Vsiqq) and one patient (0.3%) treated with aflibercept 2 mg. Retinal vasculitis was reported in one patient (0.3%) treated with Brolucizumab (Vsiqq) and no patients treated with aflibercept 2 mg.
Tabulated summary of adverse drug reactions from clinical trials: Adverse drug reactions from the HAWK and HARRIER clinical trials (Table 4) 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 4.)

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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 Brolucizumab (Vsiqq) 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 5.)

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Description of selected adverse drug 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 Brolucizumab (Vsiqq) 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 Brolucizumab (Vsiqq) suggest that patients with a medical history of intraocular inflammation and/or retinal vascular occlusion in the year prior to treatment with Brolucizumab (Vsiqq) were more likely to present with similar events after Vsiqq injection, as compared to nAMD patients with no history of these events.
Immunogenicity: As with all therapeutic proteins, there is a potential for an immune response in patients treated with Brolucizumab (Vsiqq). The immunogenicity of Brolucizumab (Vsiqq) was evaluated in serum samples. The immunogenicity data reflect the percentage of patients whose test results were considered positive for antibodies to Brolucizumab (Vsiqq) 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 Brolucizumab (Vsiqq) 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.
Wet AMD: The pre-treatment incidence of anti-brolucizumab antibodies was 35-52%. After dosing with Brolucizumab (Vsiqq) for 88 weeks, treatment-emergent anti-brolucizumab antibodies were detected in 23-25% of patients.
DME:The pre-treatment incidence of anti-brolucizumab antibodies was 64%. After dosing with Brolucizumab (Vsiqq) for 52 weeks, treatment-emergent anti-brolucizumab antibodies were detected in 12 to 18% of patients.
In wet AMD and DME, 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. Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, are immune mediated adverse events related to exposure to Brolucizumab (Vsiqq). This treatment emergent antibody response may develop following the first intravitreal injection (see PRECAUTIONS).