Already a member? Become a member Register
PCSK9 Forum

rss LinkedIn News
rss LinkedIn Latest News Updates

MENDEL

Posted on 30 July 2020 | Posted in Evolocumab
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.

Primary efficacy endpoint Percentage change from baseline in LDL-C concentration at week 12.
Other endpoints (all after 12 weeks of treatment)
  • Absolute change from baseline in LDL-C
  • Percent change from baseline in non-HDL-C
  • Percent change from baseline in ApoB
  • Percent change from baseline in the TC/high density lipoprotein cholesterol ratio
  • Percent change from baseline in ApoB/ApoA1 ratio
Key results Efficacy: Evolocumab significantly reduced LDL-C concentrations in all dose groups as follows:

Evolocumab dose LDL-C change from baseline*
70 mg every 2 weeks - 41·0% [95% CI -46·2 to -35·8]
105 mg every 2 weeks -43.9% [-49·0 to -38·7]
140 mg every 2 weeks -50·9% [-56·2 to -45·7]
280 mg every 4 weeks -39·0% [-44·1 to -34·0]
350 mg every 4 weeks -43·2% [-48·3 to -38·1]
420 mg every 4 weeks -48·0% [-53·1 to -42·9]
Placebo every 2 weeks -3·7% [-9·0 to 1·6]
Placebo every 4 weeks 4·5% [-0·7 to 9·8];
Ezetimibe -14.7% [-18·6 to -10·8]

 

*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.

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

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

 

 

Related content