Abstract 17099: Additional LDL-C Reduction Achieved With Alirocumab Dose Increase on Background Statin

Abstract

Background: The majority of ODYSSEY Phase 3 clinical trials of the PCSK9 inhibitor alirocumab (ALI) utilized a dose increase strategy designed to individualize LDL-C lowering therapy. Objective: To describe dose response in patients on background statin whose ALI dose was increased from 75 to 150 mg every 2 wks (Q2W) at wk 12. Methods: This analysis included 6 Phase 3, randomized, double-blind, double-dummy trials of 24-104 wks duration (N=1291): ALI vs placebo (COMBO I, FH I+II) or vs ezetimibe 10 mg/day (COMBO II, OPTIONS I+II). Patients on background statin with an initial dose of ALI 75 mg Q2W had dose increase to 150 mg SQ Q2W at wk 12, if at wk 8 LDL-C was ≥70 mg/dL (or >100 mg/dl in OPTIONS studies for patients without prior CHD but other risk factors). LDL-C % reductions from baseline were compared at wk 12 (before dose increase) vs wk 24, including only patients receiving study treatment (on-treatment analysis). Results: Majority of FH and high-risk patients (73.7%) achieved LDL-C <70 or <100 mg/dL (depending on CV risk) with the 75 mg Q2W dose on background statin. ALI dose was increased in 340 (26.3%) patients at wk 12 (Table). Overall, following dose increase at wk 12, an additional 14.2% reduction in LDL-C was seen at wk 24. Across the Phase 3 program, comparable AE rates were seen in patients who received dose increase vs those who did not: 65.8% vs 66.2% in placebo-controlled trials and 54.5% vs 55.9% in ezetimibe-controlled trials; injection site reactions were reported by 3.9% vs 4.9% in placebo-controlled trials and 0.9% vs 0.8% in ezetimibe-controlled trials. Conclusions: The 75 mg Q2W dose is sufficient for most patients to achieve risk-specific LDL-C goals. Increasing ALI dose from 75 to 150 mg Q2W at wk 12 was associated with a 14.2% additional reduction in LDL-C at wk 24, more than double the additional LDL-C reduction achieved by doubling a statin dose. The flexible dosing strategy allows the majority of patients to get to LDL-C goals without affecting the safety profile.