Abstract 12191: Efficacy and Safety of Long-Term Treatment With AMG 145 Monotherapy
Background: AMG 145, a fully human monoclonal antibody against PCSK9, was well tolerated and significantly reduced low-density lipoprotein cholesterol (LDL-C) either as monotherapy or combined with other lipid-lowering agents in Phase 2 studies of 12 weeks’ duration. To date, longer-term safety and efficacy of AMG 145 in hypercholesterolemic patients in the absence of concomitant statin therapy have not been reported.
Methods: We analyzed patients who completed the 12-week MENDEL study and agreed to participate in an open-label extension (OLE) study. MENDEL was a randomized, dose-ranging study that compared AMG 145 with placebo and ezetimibe in patients not on statin therapy with a 10-year Framingham risk score of ≤10%. Patients were randomized to 1 of 9 arms in approximately equal numbers: placebo, AMG 145 70, 105, or 140 mg SC every 2 weeks (Q2W); placebo, AMG 145 280, 350, or 420 mg SC every 4 weeks (Q4W); or ezetimibe 10 mg daily. OLE subjects were randomized to AMG 145 420 mg Q4W with standard of care (SOC) or SOC alone for 1 year. The primary objective was to evaluate safety and tolerability of AMG 145 on a background of SOC. Secondary objectives included effects on lipid parameters compared to MENDEL study baseline.
Results: 301 (74%) of 405 eligible MENDEL subjects enrolled in the OLE. AMG 145 was effective in reducing LDL-C in patients who had not previously received AMG 145 (n=54) and stably maintained reductions over the longer-term in patients who received AMG 145 during MENDEL. When AMG 145 was stopped, mean LDL-C returned to baseline by week 12 (Table). Adverse events rates and mean LDL-C results over the first year are shown in the table.
Conclusions: Monthly AMG 145 dosing demonstrated safety, tolerability, and sustained efficacy during prolonged treatment in hypercholesterolemic patients.
- © 2013 by American Heart Association, Inc.