Open-label ODYSSEY APPRISE study: Interim data from the first 843 participants

Background PCSK9 inhibitors (PCSK9i) have been recommended by the ESC/EAS Task Force in very high risk subjects with ASCVD and those with heterozygous familial hypercholesterolemia (HeFH) with persistent high LDL-C levels despite maximally tolerated LLT. Purpose ODYSSEY APPRISE (NCT02476006) is the first study to assess efficacy and safety at Week (W) 12 of the PCSK9i alirocumab (ALI) in a real-life setting prior to commercial availability. Methods APPRISE was an open-label, single-arm study, conducted in 16 European countries and Canada. Subjects with inadequately controlled lipid levels despite maximally tolerated LLT were included. Based on physician's judgment, participants received either ALI 75 or 150 mg every two weeks (Q2 W). Study endpoints included efficacy and safety at W12. Results This analysis included the first 843 (out of 955) participants (64% male; mean ± SD, age 57 ± 12 years; 63% with HeFH; 68% with a history of CVD). At baseline, 57% of participants were receiving high dose statin and 55% reported a history of statin tolerability issues. Baseline LDL-C (mg/dL) was 184 ± 61. ALI was initially prescribed at 75 mg Q2W in 67% of participants and 150 mg Q2W for the others. Overall, 23.5% of participants received ≥ 1 dose adjustment between baseline and W12. At W12, 52% of participants received ALI 75 mg and 48% 150 mg. LDL-C level reduction from baseline was 56% (54% in patients with HeFH and 59% without HeFH – W12 LDL-C was 83 ± 51). Adverse events were reported in 54% of participants: nasopharyngitis (5%), myalgia (4%), injection site (IS) reactions (4%), asthenia (3%), diarrhea (3%), IS erythema (2%), fatigue (2%), IS hematoma (2%) and back pain (2%) being the most common. Conclusions In a real-life setting, significant LDL-C reductions were observed with ALI 75/150 mg Q2 W in high CV risk participants. ALI was generally well tolerated. These findings are consistent with the results of ODYSSEY programme.