New add-on lipid-lowering therapy well tolerated in hypercholesterolemia patientsStein et al., J Clin Lipidol 2016
Efficacy and Safety of Gemcabene as Add-on to Stable Statin Therapy in Hypercholesterolemic Patients
Stein E, Bays H, Koren M, et al.
Journal of Clinical Lipidology 2016; published online ahead of print
BackgroundData support that each 1.0 mmol/L (38.7 mg/dL) lowering in LDL-C reduces the incidence of major coronary events, coronary revascularisations, and ischemic stroke by approximately 20% . Based on this well-established relationship, most guidelines recommend [2,3]:
- lowering of LDL-C to < 100 mg/dL (< 2.59 mmol/L) for patients at high CV risk
- lowering of LDL-C to < 70 mg/dL (< 1.81 mmol/L) in patients with established CV disease.
Gemcabene enhances the clearance of VLDL through the reduction of hepatic apolipoprotein C-III (apoC-III) messenger RNA (mRNA) [4-6]. In Phase 2 studies, gemcabene was well tolerated and resulted in significant lowering of LDL-C, apolipoprotein B (apoB), and C-reactive protein (CRP) in hypercholesterolaemia patients, and in significant lowering of triglycerides (TGs) and increase in HDL-C in hypertriglyceridaemia patients.
In this phase 2 8-week, double-blind, placebo-controlled study the efficacy and safety of gemcabene was evaluated when added to stable statin-therapy, in patients with LDL-C ≥ 130 mg/dL (3.4 mmol/L) despite statin therapy.
- Mean LDL-c (+SE) at baseline was 157.4 (5.7) in those randomised to placebo, and 149.6 (6.8) and 149.0 (6.1) in those randomised to gemcabene 300 and 900 mg respectively.
- The mean (±SE) percent LDL-C changes were: for gemcabene 300 mg (n=20): –23.4 ± 4.7% (P=0.009), for gemcabene 900 mg (n=22): –27.7 ± 4.37% (P< 0.001), for placebo (n=24): -6.2 ± 4.3%.
- The mean (±SE) percent non-HDL-C changes were: for gemcabene 300 mg: -19.8 ± 4.3% (P=0.032), for gemcabene 900mg: -23.9 ± 4.0% (P=0.004), for placebo: -6.9 ± 3.9%.
- The mean (±SE) percent apoB changes were: for gemcabene 300 mg: -11.9 ± 6.6% (P=0.301), for gemcabene 900 mg: -17.2 ± 6.0% (P=0.086), for placebo: -2.80 ± 5.7%.
- The median percent changes in CRP were: for gemcabene 300 mg: -26.1% (P=0.196), for gemcabene 900 mg: -53.9% (P<0.001), for placebo -11.1%.
- The mean (±SE) percent TG changes were: for gemcabene 300 mg: -15.6 ± 3.5% (P=0.026), for gemcabene 900 mg: -19.9 ± 3.1% (P=0.001), for placebo: -4.8 ± 3.1%.
- There was no change in HDL-C with gemcabene vs. placebo.
- Gemcabene was well tolerated. Changes in clinical laboratory assessments were small, non-significant and similar across treatment groups. There were no clinically meaningful changes in physical exams or vital signs during the study.
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The investigational lipid-lowering agent gemcabene was well tolerated in hypercholesterolemia patients on statin therapy and 300 mg and 900 mg produced significant reductions of LDL-C, non-HDL-c and CRP levels. These data support the further development of gemcabene as an add-on therapy to reduce LDL-C in patients unable to reach LDL-C goal despite statin therapy.
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