| Trial | MENDEL (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels) | ||||||||||||||||||||
| Aim | To assess the effects of evolocumab in patients with hypercholesterolaemia in the absence of concurrent lipid-lowering treatment. | ||||||||||||||||||||
| Study design | Phase 2 multicentre, double-blind randomised controlled trial | ||||||||||||||||||||
| Patient population | Patients (aged 18-75 years) in 52 centres in Europe, the USA, Canada and Australia with serum LDL-C concentrations ≥2.6 mmol/L (100 mg/dL) but <4.9 mmol/L (190 mg/dL).
A total of 406 patients were randomly assigned to subcutaneous injections of evolocumab 70 mg, 105 mg, or 140 mg, or placebo every 2 weeks; subcutaneous evolocumab 280 mg, 350 mg, or 420 mg or placebo every 4 weeks; or oral ezetimibe 10 mg/day. |
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| Primary efficacy endpoint | Percentage change from baseline in LDL-C concentration at week 12. | ||||||||||||||||||||
| Other endpoints (all after 12 weeks of treatment) |
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| Key results | Efficacy: Evolocumab significantly reduced LDL-C concentrations in all dose groups as follows:
*mean baseline LDL-C concentration 3·7 mmol/L [SD 0·6] †p<0·0001 for all doses vs placebo or ezetimibe Safety: Treatment-emergent adverse events occurred in 136 (50%) of 271 patients in the evolocumab groups, 41 (46%) of 90 patients in the placebo groups, and 26 (58%) of 45 patients in the ezetimibe group; no deaths or serious treatment-related adverse events were reported. |
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| Author conclusion | These data support the further assessment of evolocumab in long-term studies with larger and more diverse populations including patients with documented statin intolerance.
MENDEL-2 is ongoing |
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| Link | Koren MJ, Scott R, Kim JB, et al. Lancet 2012;380(9858): 1995-2006.
http://www.ncbi.nlm.nih.gov/pubmed/23141812 ClinicalTrials.gov number NCT01375777 |
