New detailed data from the phase 3 YUKAWA-2 study evaluating Evolocumab ( Repatha ), a novel investigational cholesterol-lowering medication, in Japanese patients with high cardiovascular risk and high cholesterol, were presented at the American College of Cardiology's 64th Annual Scientific Session ( ACC.15 ).
Data from the study showed subcutaneous Evolocumab 140 mg every two weeks or 420 mg monthly, compared to placebo, in combination with different daily doses of Atorvastatin ( Lipitor, Torvast ), reduced low-density lipoprotein cholesterol ( LDL-C ) by 67 to 76% from baseline at week 12 and at the mean of weeks 10 and 12.
In the YUKAWA-2 study, the most common adverse events that occurred in greater than 2% of the Evolocumab group were nasopharyngitis ( 16.8% Evolocumab; 17.8% placebo), gastroenteritis ( 3.0% Evolocumab; 1.0% placebo ) and pharyngitis ( 2.5% Evolocumab; 2.5% placebo ).
Evolocumab is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), a protein that reduces the liver's ability to remove LDL cholesterol from the blood.
In Japan, LDL cholesterol levels are not adequately controlled for many high-risk patients taking statins, nearly half of whom have not reached their LDL cholesterol goal.
YUKAWA-2 ( StudY of LDL-Cholesterol Reduction Using a Monoclonal PCSK9 Antibody in Japanese Patients With Advanced Cardiovascular Risk ) is a phase 3, multicenter, double-blind, randomized, placebo-controlled trial designed to evaluate the safety, tolerability and efficacy of Evolocumab in 404 Japanese patients with high cardiovascular risk based on the Japan Atherosclerosis Society guidelines and with hyperlipidemia or mixed dyslipidemia ( LDL cholesterol more than 100 mg/dL ).
Patients were randomized to one of eight treatment groups in a two-step randomization. Eligible patients were initially randomized to one of the following background therapies: Atorvastatin 5 mg daily or Atorvastatin 20 mg daily and entered a four-week lipid stabilization period.
At completion of lipid stabilization, patients were then randomized to one of four treatment arms: Evolocumab 140 mg every two weeks, Evolocumab 420 mg monthly, subcutaneous placebo every two weeks or subcutaneous placebo monthly.
The co-primary endpoints were the percent reduction from baseline in LDL cholesterol at week 12 and the mean percent reduction from baseline in LDL cholesterol at weeks 10 and 12.
Co-secondary efficacy endpoints included means at weeks 10 and 12 and at week 12 for the following: LDL cholesterol less than 70 mg/dL; absolute change from baseline in LDL cholesterol; and the percentage change from baseline in non-high-density lipoprotein cholesterol ( non-HDL-C ), apolipoprotein B ( ApoB ), total cholesterol ( TC ), TC/HDL-C ratio, ApoB/apolipoprotein A1 ( ApoA1 ) ratio, lipoprotein(a), triglycerides, HDL cholesterol and very low-density lipoprotein cholesterol ( VLDL-C ). ( Xagena )
Source: Amgen, 2015