Abstract 12621: Efficacy and Tolerability of Long-Term Treatment With AMG 145 in Patients With Statin Intolerance
Background: In the GAUSS Phase 2 12-week placebo-controlled trial in statin-intolerant patients, AMG 145, a monoclonal antibody to PCSK9, was well tolerated and achieved dose dependent LDL-C reductions of 41%-63%. Patients completing the trial were eligible for an open-label long-term extension (OLE).
Methods: The extension trial (NCT01439880) re-randomized patients 2:1 to either AMG 145 420 mg every 4 weeks with standard of care (SOC) or SOC alone for one year. The primary objective was to compare the safety and tolerability of the two therapies. Secondary objectives included comparison of long-term effects on lipid parameters.
Results: Of 157 patients in the GAUSS trial, 126 (80%) entered into the OLE; 80 received AMG 145/SOC and 46, SOC. The mean (standard error) baseline LDL-C by ultracentrifugation based on entry into the original trial was 194 (6) mg/dL for the AMG 145 group and 195 (8) mg/dL for the SOC group. During follow-up, 3 (4%) of AMG 145/SOC and 2 (4%) of SOC-treated patients discontinued treatment. Mean percentage reductions in LDL C by ultracentrifugation and Lp(a) with AMG 145, shown in the Table, exceeded 50% and 24% respectively, at all time points. Changes in other lipids and lipoproteins were consistent with changes in the original 12-week GAUSS trial. Adverse event rates over the first year were 91.3% for the AMG 145/SOC group and 82.6% for the SOC group (Table). ALT/AST >3x ULN was reported in two patients treated with AMG 145/SOC and was sustained in one patient who had ALT/AST >3x ULN at OLE entry. None had ALT or AST >5x ULN. No patients in the AMG 145/SOC group and two in the SOC group had CK elevations >5x ULN, which were not sustained on repeat analysis.
Conclusions: In patients with well-documented muscle-related side effects, long-term treatment with AMG 145 420 mg every 4 weeks continued to be well tolerated. Reductions in LDL cholesterol of >50% and Lp(a) of >24% were maintained.
- © 2013 by American Heart Association, Inc.