US-based biotechnology firm Amgen has released positive top-line results from Phase III MENDEL-2 trial of an investigational fully human monoclonal antibody, evolocumab (AMG 145) in patients with high cholesterol.
The MENDEL-2 (‘Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2’) trial met its co-primary endpoints, which include the percent reduction from baseline in low-density lipoprotein cholesterol (LDL-C) at week 12 and the mean percent reduction from baseline in LDL-C at weeks ten and 12.
The mean percent reductions in LDL-C, or bad cholesterol, compared to placebo and ezetimibe were consistent with results observed in the MENDEL Phase II trial.
Evolocumab inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver’s ability to remove LDL-C from the blood.
The randomised, multi-centre, double-blind, double-dummy, stratified, placebo and ezetimibe-controlled parallel group trial assessed safety, tolerability and efficacy of evolocumab in 614 patients with high cholesterol who were not receiving lipid-lowering therapy.
In the trial, patients were given one of six treatment groups to compare two dosing regimens of evolocumab (140mg every two weeks or 420mg monthly) with placebo and ezetimibe (10mg daily).
The company said that safety was balanced across treatment groups in the trial and the most common adverse events (AEs) observed were headache, diarrhoea, nausea and urinary tract infection.
Amgen executive vice president of R&D Sean Harper said data from the MENDEL-2 monotherapy trial carried out on more than 600 patients provide the first of Phase III results from the company’s comprehensive development program for evolocumab.
"The positive results we have seen with two distinct dosing options suggest that evolocumab may offer a promising approach to treat patients with high cholesterol," Harper said.
According to the Centers for Disease Control and Prevention, more than 71 million adults in the US have high LDL-C, which is recognised as a major risk factor for cardiovascular disease.