Majority of hypercholesterolaemia patients reaches target LDL-c with evolocumabNews - Apr. 1, 2014
LDL-C Assessment w/ PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy-2 (LAPLACE-2)
BackgroundDespite the efficacy of statins, their effect are not sufficient for all patients. Many patients do not achieve target levels for LDL-c with high doses of statins, and need other LDL-lowering medication. Evolocumab (AMG 145) is a human antibody against PCSK9. In phase 2 studies evolocumab was well tolerated and showed robust LDL-c reductions.
In this randomised, multicenter study the tolerability and efficacy with respect to LDL-c of evolocumab was evaluated, in comparison to both placebo and ezetimibe, in hypercholesterolaemic participants on statins. The primary endpoint was percent change in LDL-c levels from baseline, after 12 weeks of treatment with a biweekly (140 mg, Q2W) of monthly (420 mg, Q4W) subcutaneous dose of evolocumab in addition to statin treatment, relative to placebo or ezetimibe.
- The mean reduction of LDL-c after 10 and 12 weeks was 63-75% with evolocumab (Q2W and Q4W), in comparison to placebo, while ezetimibe gave a reduction of 19-32% relative to placebo. This was seen in combination with more or less intensive statin regimes.
- In contrast to in the other treatment regimes, treatment with evolocumab caused the majority of patients to achieve target LDL-c (<70 mg/dL), both in Q2W and Q4W (86-94% with moderately intense and 93-95% with intense statin treatment).
- Strong reductions were also seen with evolocumab in non-HDL cholesterol (-58-65%) and ApoB (-51-59%) (Q2W and Q4W), irrespective of statin regime. Reductions with ezetimibe were around 20% and 30% for non-HDL-c and ApoB respectively.
- Lipoprotein(a) diminished with 21-36% on evolocumab (Q2W and Q4W, irrespective of statin regime), while other treatments did not show reductions.
- Evolocumab was tolerated at least as well as the statin and ezetimibe treatments.
ConclusionEvolocumab yielded strong reductions of LDL-c in the average of week 10 and 12, in patients with hypercholesterolaemia who receive statin treatment, more so than ezetimibe plus statins, or placebo and statins. No differences were seen in the effect of evolocumab between more or less intensive statin therapies. Q2W and Q4W treatments of evolocumab were clinically equivalent. The majority of patients on evolocumab reached LDL-c targets. Safety and tolerability of evolocumab was comparable with placebo en ezetimibe treatment.