ACC: Evolocumab may help reduce LDL cholesterol levels

Results of 5 phase 3 studies evaluating evolocumab (AMG 145), an investigational fully human monoclonal antibody that inhibits PCSK9, a protein that reduces the liver’s ability to remove low-density lipoprotein cholesterol (LDL-C), or “bad” cholesterol, from the blood, were presented at the American College of Cardiology’s 63^rd Annual Scientific Session (ACC.14), in Washington, D.C

The data presented are part of Amgen's large and comprehensive evolocumab clinical trial program, PROFICIO (Program to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different POpulations), which is evaluating evolocumab in 20 clinical trials, with a combined planned enrollment of nearly 30,000 patients.

Results from the 5 phase 3 studies consistently demonstrated statistically significant reductions in LDL-C across a number of at-risk patient groups with elevated cholesterol. The trials evaluated evolocumab administered every 2 weeks and monthly in combination with statins in patients with hyperlipidemia (LAPLACE-2); in patients with hyperlipidemia who cannot tolerate statins (GAUSS-2); as a monotherapy in patients with high cholesterol (MENDEL-2); and in combination with statins and other lipid-lowering therapies in patients whose elevated cholesterol is caused by a genetic disorder called heterozygous familial hypercholesterolemia (RUTHERFORD-2). Additionally, the DESCARTES study evaluated evolocumab administered monthly as a long-term 52-week therapy in patients with high cholesterol on risk-based lipid lowering therapy.

“The positive results . . . show that evolocumab could be a promising lipid-lowering treatment for patients with high cholesterol who struggle to keep their LDL-C levels under control despite currently available treatments,” said LAPLACE-2 lead investigator Jennifer G. Robinson, MD, MPH, director of the Prevention Intervention Center, professor of the Departments of Epidemiology & Medicine, College of Public Health at the University of Iowa. “While statins are effective in reducing LDL cholesterol levels and the risk of heart attack and stroke, some patients still need more LDL-lowering treatment options.” 

Cardiovascular disease (CVD) is the number 1 cause of death worldwide and major cardiovascular events lead to increased direct healthcare costs, including hospitalizations and CVD-related procedures. Overall, the total direct and indirect cost of CVD in the U.S. for 2010 is estimated to be $444.2 billion.

Findings from the 5 studies evaluating evolocumab presented at ACC.14 are as follows:

• Results from the 12-week, 307-patient GAUSS-2 study showed in patients who could not tolerate effective doses of at least 2 different statins due to muscle-related side effects, treatment with subcutaneous evolocumab (140 mg every 2 weeks or 420 mg monthly), significantly reduced mean LDL-C by 37% to 39% from baseline compared to ezetimibe (P<.001). In the GAUSS-2 study, the most common adverse events (AEs) (≥5% in the combined evolocumab group) were headache, myalgia, pain in extremity, and muscle spasms.

• Results from the 12-week, 1,896-patient LAPLACE-2 study showed treatment with subcutaneous evolocumab (140 mg every 2 weeks or 420 mg monthly) in combination with different daily doses of statin therapy significantly reduced mean LDL-C by 55% to 76% from baseline compared to placebo and 38% to 47% from baseline compared to ezetimibe (P<.001). In the LAPLACE-2 study, no AEs occurred in ≥2% of the evolocumab combined group. The most common AEs in the evolocumab combined group (>1.5%) were back pain, arthralgia, headache, muscle spasms, and pain in extremity.

• Results from the 12-week, 614-patient MENDEL-2 study showed treatment with subcutaneous evolocumab (140 mg every 2 weeks or 420 mg monthly) in patients who were not receiving lipid-lowering therapy significantly reduced mean LDL-C by 55% to 57% from baseline compared to placebo and 38% to 40% from baseline compared to ezetimibe (P<.001). In MENDEL-2, the most common AEs (≥2 percent in evolocumab combined group) were headache, diarrhea, nausea, and urinary tract infection. 

• Results from the 52-week, 901-patient DESCARTES study showed in patients with high LDL-C and a range of cardiovascular risk, evolocumab 420 mg subcutaneous monthly reduced mean LDL-C by 57% from baseline at week 52 compared to placebo (P<.001). The most common AEs (>5% in evolocumab) in the DESCARTES study were nasopharyngitis, upper respiratory tract infection, influenza and back pain.

• Results from the 12-week, 329-patient RUTHERFORD-2 study showed that in patients with heterozygous familial hypercholesterolemia (HeFH) on a stable dose of statin and other lipid-lowering therapies, treatment with subcutaneous evolocumab significantly reduced mean LDL-C by 59% to 66% from baseline compared to placebo (P<.001). In RUTHERFORD-2, the most common AEs (≥2% in the combined evolocumab group) were nasopharyngitis, headache, contusion (ie, bruise), back pain, nausea, arthralgia, upper-respiratory tract infection, influenza, myalgia, and pain in extremity.

The DESCARTES study was simultaneously published in the New England Journal of Medicine, and the MENDEL-2 and GAUSS-2 studies were simultaneously published in the Journal of the American College of Cardiology.