Praluent Adverse Reactions

Summary of the safety profile: Most common adverse reactions were local injection site reactions, upper respiratory tract signs and symptoms, and pruritus. Most common adverse reactions leading to treatment discontinuation in patients treated with Praluent were local injection site reactions.
No difference in the safety profile was observed between the two doses (75 mg and 150 mg) used in the phase 3 program.
Tabulated list of adverse reactions: Adverse reactions are presented by system organ class. Frequency categories are defined as: 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) and not known (cannot be estimated from the available data).
The following adverse reactions were reported in patients treated with alirocumab in pooled controlled studies: see Table 2.

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Description of selected adverse reactions: Local injection site reactions: Local injection site reactions, including erythema/redness, itching, swelling, and pain/tenderness, were reported in 6.1% of patients treated with alirocumab versus 4.1% in the control group (receiving placebo injections). Most injection site reactions were transient and of mild intensity. The discontinuation rate due to local injection site reactions was comparable between the two groups (0.2% in the alirocumab group versus 0.3% in the control group).
General allergic reactions: General allergic reactions were reported more frequently in the alirocumab group (8.1% of patients) than in the control group (7.0% of patients), mainly due to a difference in the incidence of pruritus. The observed cases of pruritus were typically mild and transient. In addition, rare and sometimes serious allergic reactions such as hypersensitivity, nummular eczema, urticaria, and hypersensitivity vasculitis have been reported in controlled clinical studies. (See Precautions.)
Special populations: Elderly: Although no safety issues were observed in patients over 75 years of age, data are limited in this age group. In controlled studies, 1158 patients (34.7%) treated with Praluent were ≥65 years of age and 241 patients (7.2%) treated with Praluent were ≥75 years of age. There were no significant differences observed in safety and efficacy with increasing age.
Every 4 week dosing study: The safety profile in patients treated with a 300 mg once every 4 week (monthly) dosing regimen, was similar to the safety profile as described for the clinical studies program using a 2 week dosing regimen, except for a higher rate of local injection site reactions. Local injection site reactions were reported overall at a frequency of 16.6% in the 300 mg once every 4 weeks treatment group and 7.9% in the placebo group. Patients in the alirocumab 300 mg every 4 weeks treatment group received alternating placebo injections to maintain blinding in regard to injection frequency. Excluding injection site reactions (ISRs) that occurred after these placebo injections, the frequency of ISRs was 11.8%. The discontinuation rate due to injection site reactions was 0.7% in the 300 mg once every 4 weeks treatment group and 0% in the placebo group.
LDL-C values <25 mg/dL (<0.65 mmol/L): In pooled controlled studies using an every 2 week dosing interval, 796 of 3340 patients (23.8%) treated with Praluent had two consecutive values of LDL-C <25 mg/dL (<0.65 mmol/L), including 288 patients (8.6%) with two consecutive values <15 mg/dL (<0.39 mmol/L). These mostly occurred when patients were initiated and maintained on 150 mg Q2W of Praluent regardless of the baseline LDL-C value or the response to treatment.
In the every 4 week dosing study, 113 of 458 patients (24.7%) treated with 300 mg every 4 weeks/150 mg every 2 weeks had two consecutive calculated LDL-C values <25 mg/dL (<0.65 mmol/L), and 45 of 458 patients (9.8%) had two consecutive calculated LDL-C values <15 mg/dL (<0.39 mmol/L).
No adverse reaction was identified related to these LDL-C values.
Immunogenicity/Anti-drug-antibodies (ADA): In phase 3 studies, 4.8% of patients treated with alirocumab 75 mg and/or 150 mg every 2 weeks exhibited an ADA response after initiating treatment as compared to 0.6% in the control group (placebo or ezetimibe). The majority of those patients exhibited transient low-titer ADA responses with no neutralising activity. Compared to patients who were ADA negative, patients with an ADA positive status did not exhibit any difference in alirocumab exposure, efficacy, or safety, except for a higher rate of injection site reactions. Only 1.2% of patients exhibited neutralising antibodies (NAb), all of them in the alirocumab group. Most of these patients had only one positive neutralising sample. Only 10 patients (0.3%) had two or more NAb positive samples. The data do not suggest a correlation between the presence of NAb and LDL-C lowering efficacy or safety.
In the every 4 week dosing study, 4.7% of patients treated with alirocumab 300 mg once every 4 weeks/150 mg every 2 weeks exhibited an ADA response as compared to 2.6% of patients treated with placebo. In this study, patients treated with alirocumab who developed ADA had a lower incidence of injection site reactions compared with patients who did not develop ADA (8.6% vs 16.2%). 0.4% of patients treated with alirocumab 300 mg every 4 weeks/150 mg every 2 weeks developed neutralizing antibodies (NAb) on at least one occasion with no loss of efficacy observed; no NAb were observed in patients treated with control.
Immunogenicity data are highly dependent on the sensitivity and specificity of the ADA assay.
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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.
Postmarketing Experience: The following adverse reactions have been reported during post-approval use of Praluent. The adverse reactions are derived from spontaneous reports and therefore, the frequency is "not known" (cannot be estimated from the available data).
General disorders and administration site conditions: Flu-like illness.
Skin and subcutaneous tissue disorders: Angioedema.