Sybrava Adverse Reactions

Summary of the safety profile: The safety of inclisiran was evaluated in 3 Phase III placebo-controlled trials that included 3,655 patients with atherosclerotic cardiovascular disease (ASCVD), ASCVD risk equivalents, or familial hypercholesterolemia, treated with maximally tolerated statins and inclisiran or placebo, including 1,833 patients exposed to inclisiran for up to 18 months (mean treatment duration of 526 days).
Safety data from the 3 Phase III placebo-controlled pivotal trials showed that treatment-emergent adverse events (TEAEs) occurred at a similar incidence in the inclisiran-treated and placebo-treated patients. The majority of the TEAEs were mild and unrelated to inclisiran or placebo. The only adverse reactions associated with inclisiran in pivotal trials were adverse events at the injection site.
Tabulated summary of adverse drug reactions from clinical trials: Adverse drug reactions from 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. 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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Description of selected adverse drug reactions: Adverse events at the injection site: Adverse events at the injection site occurred in 8.2% and 1.8% of inclisiran-treated and placebo-treated patients, respectively, in the pivotal trials. The proportion of patients who discontinued treatment due to adverse events at the injection site in inclisiran-treated patients and placebo-treated patients were 0.2% and 0.0%, respectively. All of these adverse drug reactions were mild or moderate in severity, transient and resolved without sequelae. The most frequently occurring adverse events at the injection site in patients treated with inclisiran were injection site reaction (3.1%), injection site pain (2.2%), injection site erythema (1.6%), and injection site rash (0.7%).
Immunogenicity: In the pivotal trials, 1,830 patients were tested for anti-drug antibodies. Confirmed positivity was detected in 1.8% (33/1830) of patients prior to dosing and in 4.9% (90/1830) of patients during the 18 months of treatment with inclisiran. No clinically significant differences in the clinical efficacy, safety or pharmacodynamic profiles of inclisiran were observed in the patients who tested positive for anti-inclisiran antibodies.